The diverse chemistry of protoplanetary disks as revealed by JWST.

Early results from the James Webb Space Telescope-Mid-InfraRed Instrument (JWST-MIRI) guaranteed time programs on protostars (JOYS) and disks (MINDS) are presented. Thanks to the increased sensitivity, spectral and spatial resolution of the MIRI spectrometer, the chemical inventory of the planet-forming zones in disks can be investigated with unprecedented detail across stellar mass range and age. Here, data are presented for five disks, four around low-mass stars and one around a very young high-mass star. The mid-infrared spectra show some similarities but also significant diversity: some sources are rich in CO2, others in H2O or C2H2. In one disk around a very low-mass star, booming C2H2 emission provides evidence for a "soot" line at which carbon grains are eroded and sublimated, leading to a rich hydrocarbon chemistry in which even di-acetylene (C4H2) and benzene (C6H6) are detected. Together the data point to an active inner disk gas-phase chemistry that is closely linked to the physical structure (temperature, snowlines, presence of cavities and dust traps) of the entire disk and which may result in varying CO2/H2O abundances and high C/O ratios >1 in some cases. Ultimately, this diversity in disk chemistry will also be reflected in the diversity of the chemical composition of exoplanets.

Abundant hydrocarbons in the disk around a very-low-mass star.

Very-low-mass stars (those less than 0.3 solar masses) host orbiting terrestrial planets more frequently than other types of stars. The compositions of those planets are largely unknown but are expected to relate to the protoplanetary disk in which they form. We used James Webb Space Telescope mid-infrared spectroscopy to investigate the chemical composition of the planet-forming disk around ISO-ChaI 147, a 0.11-solar-mass star. The inner disk has a carbon-rich chemistry; we identified emission from 13 carbon-bearing molecules, including ethane and benzene. The high column densities of hydrocarbons indicate that the observations probe deep into the disk. The high carbon-to-oxygen ratio indicates radial transport of material within the disk, which we predict would affect the bulk composition of any planets forming in the disk.

Relations between cardiac and vascular structure in patients with primary and secondary hypertension.

BACKGROUND: Data on cardiac and vascular structure in secondary hypertension are generally scarce, and no data on the interrelations between cardiac mass and structural characteristics of the vessel wall, both in large and in small resistance arteries, are presently available. OBJECTIVES: The aim of this study was to investigate the relation between structural changes in subcutaneous small arteries, left ventricular mass and wall thickness of the common carotid artery in patients with primary and secondary hypertension. METHODS: Seventy-four subjects were included in the study: 11 patients with pheochromocytoma, 14 with primary aldosteronism (PA), 19 with renovascular hypertension (RVH), 18 with essential hypertension (EH) and 12 normotensive (NT) control subjects. All subjects were submitted to a biopsy of subcutaneous fat. Morphologic characteristics of subcutaneous small resistance arteries (relaxed diameter <300 microm) were directly evaluated using a micromyographic technique. All subjects were submitted to calculation of left ventricular mass index (LVMI) and common carotid artery intima-media thickness (CCIMT), using ultrasound technique. RESULTS: The correlation coefficients between the media to lumen ratio in subcutaneous small arteries (M/L) and LVMI or between M/L and CCIMT were closer in RVH than in pheochromocytoma, EH or NT; in PA the correlation coefficients were slightly less close than those in RVH. An excess prevalence of carotid plaques in RVH was observed. CONCLUSIONS: A close relation between small resistance artery morphology and cardiac or carotid artery structure may be observed in those hypertensive patients in whom the renin-angiotensin-aldosterone system is activated. In constrast, in NT, EH and pheochromocytoma no significant correlation between M/L and LVMI or CCIMT was observed.

Delayed development of hypertension after short-term nitrendipine treatment.

In this study we evaluated the delayed effects of a calcium entry blocker on blood pressure and on vascular structural and functional alterations in mesenteric resistance arteries of spontaneously hypertensive rats (SHR). The calcium entry blocker nitrendipine was administered (30 mg/kg per day) according to three different schedules: in one group of SHR from 4 to 8 weeks of age (n = 12), in a second group from 8 to 12 weeks of age (n = 12), and in a third group from 4 to 12 weeks of age (n = 12). Twelve untreated SHR and 12 untreated Wistar-Kyoto rats served as controls. Half the animals of each group were killed at 13 weeks, and the remaining were killed at 38 weeks. After death, relative left ventricular mass was calculated. Vascular morphology and function (responses to norepinephrine and acetylcholine) in mesenteric small arteries were then assessed using a micromyographic technique. Nitrendipine treatment delayed the development of hypertension and determined the regression of structural alterations of mesenteric resistance arteries in SHR. These favorable effects were maintained for several weeks after treatment withdrawal, provided that treatment was started at 4 weeks of age. Considering the functional alterations of mesenteric arteries in SHR (responses to norepinephrine and acetylcholine), nitrendipine treatment determined an improvement of both these dysfunctions as long as reductions of the media-to-lumen ratio and blood pressure, respectively, were maintained.

Effects of low and high doses of fosinopril on the structure and function of resistance arteries.

It has been suggested that angiotensin-converting enzyme inhibitors may induce a significant regression of cardiovascular hypertrophy not only through blood pressure reduction but also as a possible consequence of growth factor inhibition. The aim of this study was to evaluate the effects of the angiotensin-converting enzyme inhibitor fosinopril, given either at a hypotensive high dose or a nonhypotensive low dose, on structural and functional alterations of mesenteric resistance arteries and on cardiac mass in spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats. Fosinopril was administered in the drinking water from 6 to 12 weeks of age. Rats were killed at 12 weeks, and the ratio of heart weight to body weight was measured. Mesenteric arterioles were dissected and mounted on a micromyograph (Mulvany's technique). Vascular morphology (media-lumen ratio, media thickness) and endothelial function (response to acetylcholine) were then assessed. During the 6 weeks of treatment, systolic pressure in SHR treated with high-dose fosinopril was significantly lower compared with that in untreated SHR, whereas no difference was observed with low-dose fosinopril. In SHR treated with both high-dose and low-dose fosinopril, a statistically significant reduction of vascular structural alterations, in terms of both media-lumen ratio and media thickness, was observed. The ratio of heart weight to body weight was reduced only in SHR treated with high-dose fosinopril. An improvement in the endothelium-dependent relaxation to acetylcholine was observed in SHR treated with high-dose fosinopril compared with untreated SHR, whereas in SHR treated with low-dose fosinopril no improvement in endothelial function was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac and vascular structural changes. Prevalence and relation to ambulatory blood pressure in a middle-aged general population in northern Italy: the Vobarno Study.

The aims of this study were to determine the prevalence of structural changes in the carotid arteries and heart and the correlation between these changes and the commonly recognized cardiovascular risk factors in the general population. Structural changes in the carotid arteries were defined as the intima-media thickness of the artery measured by B-mode ultrasound. Changes in the heart were defined as left ventricular mass index (LVMI) measured by echocardiography. LVMI values greater than 134 g/m2 in men and greater than 110 g/m2 in women were considered abnormal, indicating the presence of left ventricular hypertrophy. Blood pressure (BP) was measured in the clinic setting with a mercury sphygmomanometer and by 24-hour noninvasive ambulatory monitoring. Hypertension was defined as a sustained systolic BP greater than or equal to 160 mm Hg and/or diastolic BP increase greater than or equal to 95 mm Hg. The study population consisted of 225 subjects (107 women and 118 men) 48 to 64 years old. Prevalence of intima-media thickening (intima-media thickness > 1 mm) was 11% in normotensive subjects and 44% in hypertensive subjects. The presence of plaque (wall thickening with either mineralization or focal protrusion in the lumen at least 50% greater than the surrounding wall, usually > 2 mm) was observed in 35% of normotensive subjects and 44% of hypertensive subjects. The prevalence of left ventricular hypertrophy was 13% in normotensive subjects and 19% in hypertensive subjects. Intima-media thickness in the common and bifurcation segments of carotid arteries correlated well with LVMI (r = .20 and r = .19, respectively; P < .01). Intima-media thickness and LVMI were both positively related to 24-hour monitored BP (P < .01). However, in the multivariate analysis, body mass index (P = .027), sex (P < .001), and 24-hour mean BP (P = .025) were the most significant determinants of LVMI, whereas carotid artery intima-media thickness was found to be associated best with age (P < .001), cigarette smoking (P = .009), serum cholesterol (P = .025), serum glucose (P = .038), and nighttime systolic BP (P = .006). Logistic regression analysis confirmed the association between the presence of plaque and age (P < .001), nighttime systolic BP (P < .05), and cigarette smoking (P < .05); a negative association between plaque and the decrease in mean systolic BP daytime to nighttime was also observed (P < .001). In conclusion, in a general population of unselected middle-aged subjects, carotid wall thickness and LVMI were associated with each other and related to 24-hour BP levels although the major determinants of carotid wall and cardiac structure were different.

Vascular hypertrophy and remodeling in secondary hypertension.

It has been proposed that several neurohumoral factors may be involved in the genesis of vascular structural changes (remodeling or hypertrophy) frequently observed in essential hypertension. Therefore, in this study we investigated vascular structural alterations of subcutaneous small resistance arteries in patients with secondary forms of hypertension. The study included 70 participants: 11 with pheochromocytoma, 13 with primary aldosteronism, and 17 with renovascular hypertension; 13 normotensive subjects and 16 patients with essential hypertension served as controls. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph, and media-lumen ratio, media thickness, remodeling index, and growth index were evaluated. Endothelial function was evaluated according to the dose-response curve to acetylcholine. In patients with either primary aldosteronism or renovascular hypertension, a marked increase in media-lumen ratio was observed, whereas in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in patients with essential hypertension. The increase in media-lumen ratio in patients with essential hypertension and with pheochromocytoma was mainly due to vascular remodeling (remodeling index, 93% to 94%), whereas in patients with renovascular hypertension, there was vascular growth (remodeling index, 70%; growth index, 53%). Patients with primary aldosteronism had an intermediate pattern compared with the other two forms of secondary hypertension. An evident impairment of endothelial function was observed in all four hypertensive groups. In conclusion, the renin-angiotensin-aldosterone system seems to be more powerful than the adrenergic system in inducing vascular growth.

Angiotensin II type 1 receptor A/C1166 polymorphism. Relationships with blood pressure and cardiovascular structure.

The angiotensin II type 1 (AT1) receptor has a key role in mediating the vasoconstrictor and growth-promoting effects of angiotensin II. It has been reported that a polymorphism of the AT1 receptor gene (an A/C transversion at position 1166) may be associated with cardiovascular phenotypes, such as arterial blood pressure and aortic stiffness, that underlie a condition of increased cardiovascular risk. We examined a sample of 212 subjects randomly selected from a general population in northern Italy to investigate the role of AT1 receptor gene polymorphism, in the regulation of blood pressure and cardiovascular growth. We measured blood pressure (both clinic and 24-hour ambulatory recording), left ventricular mass (echocardiography), and carotid artery wall thickness (B-mode ultrasound); we assessed the AT1 receptor genotype by polymerase chain reaction and allele-specific oligonucleotide hybridization. Blood pressure values were lower in CC homozygotes than in heterozygotes and AA homozygotes; the difference was statistically significant for clinic measurements (mean difference for mean blood pressure, -6.6 mm Hg, P = .01; 95% confidence interval, -1.6 to -11.7 mm Hg) but not for ambulatory blood pressure measurements. CC homozygotes also presented a lower incidence of a positive family history of hypertension (P = .027). No statistically significant differences among AT1 receptor A/C1166 genotypes were observed for left ventricular mass or carotid artery wall thickness. We conclude that the present study does not support a major role of the AT1 receptor gene A/C1166 polymorphism as a marker of conditions associated with increased cardiovascular risk.

Endothelial dysfunction in hypertension is independent from the etiology and from vascular structure.

The aim of our study was to evaluate the relationships between endothelial function, small resistance artery structure, and blood pressure in patients with primary or secondary hypertension. Sixty subjects were included in the study: 9 patients with pheochromocytoma, 10 with primary aldosteronism, 17 with renovascular hypertension, and 13 with essential hypertension with 11 normotensive subjects who served as controls. Clinic and 24-hour ambulatory blood pressure (ABPM) were evaluated. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph and the media/lumen ratio was calculated. A dose-response curve to acetylcholine was performed at cumulative concentrations from 10(-9) to 10(-5) mol/L. The vasodilator response to acetylcholine was similarly impaired in the four groups of hypertensive patients (ANOVA P<.05 versus normotensive controls), without any significant difference among them. In subcutaneous small arteries of patients with either primary aldosteronism or renovascular hypertension, a marked increase in media:lumen ratio was observed, while in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in essential hypertension. No significant correlation between media-lumen ratio or clinic blood pressure and maximum acetylcholine-induced vasodilatation was observed. On the contrary, a significant, albeit not very close, correlation between ABPM values and maximum acetylcholine-induced vasodilatation was observed (r=34, P<.05 with 24-hour systolic blood pressure, r=0.36, P<.05 with 24-hour diastolic blood pressure). In conclusion, endothelial dysfunction seems to be independent from the degree of vascular structural alterations and from the etiology of hypertension, and it is probably more linked to the hemodynamic load.

Effects of losartan and enalapril on small artery structure in hypertensive rats.

We evaluated the effects on cardiovascular structure of the angiotensin-converting enzyme (ACE) inhibitor enalapril and of the angiotensin II receptor blocker losartan, administered either at hypotensive or nonhypotensive dosage in spontaneously hypertensive rats (SHR). SHR were treated from ages 4 to 12 weeks with low-dose (1 mg x kg(-1) x d(-1)) enalapril, low-dose (0.5 mg x kg(-1) x d(-1)) losartan, high-dose (25 mg x kg(-1) x d(-1)) enalapril, or high-dose (15 mg x kg(-1) x d(-1)) losartan. Untreated WKY and SHR were also studied. Rats were killed at 13 weeks of age, and the heart was weighed. Mesenteric small arteries were dissected and mounted on a micromyograph for determination of media thickness and lumen diameter. In fixed arteries, cell volume, number of cells per segment length, and number of cell layers were measured using the unbiased "disector" method. Systolic blood pressure was significantly reduced by the high doses of both drugs, but the hypotensive effect was greater with enalapril than with losartan (P<0.05). In the high-dose enalapril and losartan groups, there were similar reductions in relative left ventricular mass, media/lumen ratio, and number of cell layers of resistance arteries; however, there were no differences in the cell volume or number of cells per segment length of resistance arteries. Low-dose enalapril did not affect systolic blood pressure or any of the structural parameters. The results show that the hypotensive effects of both losartan and enalapril were associated with outward remodeling of resistance arteries at the cellular level. The effect of losartan on resistance artery structure was equal to that of enalapril, despite the smaller hypotensive effect.

The vasoconstriction induced by endothelin-1 is mediated only by ET(A) receptors in mesenteric small resistance arteries of spontaneously hypertensive rats and Wistar Kyoto rats.

OBJECTIVE: To evaluate the functional responses of mesenteric small resistance arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rat controls to endothelin-1 (ET-1), in the presence and absence of an ET(A) receptor antagonist drug as well as to an ET(B) receptor agonist. METHODS: Twenty rats aged 12 weeks were studied. They were 10 SHR and 10 WKY rats. Mesenteric small resistance arteries (relaxed diameter 100-180 microm) were dissected and mounted on a micromyograph (Mulvany's technique). A dose-response curve for response to ET-1 was plotted for cumulative concentrations (from 10(-11) to 10(-8) mol/l) in the presence and absence of 10(-6) mol/l FR 139317 (a selective antagonist of ET(A) receptors). In addition, the effects of 10(-7) mol/l N-succinyl-[Glu9, Ala11,15]-endothelin 1 fragment 8-21 (IRL 1620, a selective agonist of ET(B) receptors) were evaluated. RESULTS: The response of ET-1 was greater in WKY rats than it was in SHR. Almost all the vasoconstrictor effect of ET-1 could be prevented by addition of FR 139317, whereas the agonist of ET(B) receptors had no effect (no change in active force). CONCLUSIONS: The contractile effects of ET-1 on mesenteric small resistance arteries of SHR and WKY rats are mediated mostly by ET(A) receptors, whereas ET(B) receptors play a minor role, if any. It is possible, however, that a vasoconstrictor effect of ET(B) receptors on the smooth muscle could be masked by the concomitant stimulation of endothelial ET(B) vasodilator receptors.

Power spectral analysis of the heart rate in hypertensive patients with and without left ventricular hypertrophy: the effect of a left ventricular mass reduction.

OBJECTIVE: The aim of this study was to evaluate the spectral analysis of the heart rate in normotensive subjects and in hypertensive patients with and without left ventricular hypertrophy (LVH), under basal conditions and after a reduction in left ventricular mass. SUBJECTS AND METHODS: In 12 normotensive subjects and 22 hypertensive patients (14 with and eight without LVH), we performed 24 h electrocardiogram Holter monitoring, ambulatory blood pressure monitoring and an echocardiographic study. Sequences of 512 R-R intervals, during daytime, afternoon and night-time periods, were taken for an evaluation of spectral analysis (Box-Jenkins method). We then calculated the absolute and percentage power spectral density of the peak centred at 0.10 Hz (low-frequency peak) and at 0.25 Hz (high-frequency peak). RESULTS: At baseline, a daytime to night-time decrease in the low-frequency peak was detected in normotensives (P < 0.01) and in hypertensives without LVH (P < 0.01), while no change was observed in hypertensives with LVH. The power spectral density low-frequency peak during the daytime and night-time was significantly greater in hypertensives with LVH than in those without LVH (P < 0.001) and in normotensive subjects (P < 0.001). Fourteen of these patients with LVH were given effective long-term antihypertensive treatment and were studied again 20 days after the treatment had been withdrawn, when blood pressure had increased to pretreatment values. In eight patients showing a reduction in LVH, we found a significant decrease in the power spectral density low-frequency peak and an increase in the high-frequency peak during daytime and night-time in respect to basal conditions, and circadian variations in the spectral indices of heart rate variability were restored. In contrast, in six patients without reversal of LVH, the power spectral density low-frequency peak did not change in respect to basal conditions and remained significantly higher in comparison with the patients with LVH regression. CONCLUSION: A reduction in LVH may be associated with restoration of daytime to night-time cardiac autonomic control, as evaluated by a power spectral analysis of the heart rate.

Gene expression of cardiac beta 1-adrenergic receptors during the development of hypertension in spontaneously hypertensive rats.

OBJECTIVE: To study adrenergic receptors in the heart tissues of genetically hypertensive rats by evaluating the gene expression and the membrane protein density of beta 1-adrenergic receptors using steady-state messenger RNA (mRNA) levels and a radioligand binding assay, respectively. DESIGN: We compared prehypertensive (5-week-old) and early-hypertensive (13-week-old) spontaneously hypertensive rats (SHR) with age-matched Wistar-Kyoto (WKY) normotensive control rats. METHODS: Polyadenylated RNA was extracted from individual hearts and analysed by the slot-blot technique using a beta 1-adrenergic receptor complementary DNA probe. beta-Adrenergic receptors in myocardial membranes were studied by radioligand binding assay using [125I]-cyanopindolol and the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively. RESULTS: beta 1-Adrenergic receptor mRNA levels were slightly higher, and membrane protein density was similar in prehypertensive SHR and age-matched WKY rats. However, both beta 1-adrenergic receptor mRNA levels and beta 1-adrenergic receptor density were lower in the hypertensive SHR than in the control rats. beta 1-Adrenergic receptor mRNA was significantly reduced in older rats of both strains, and this reduction was most evident in the SHR. CONCLUSIONS: The absence of downregulation of beta 1-adrenergic receptors in young SHR, despite published data indicating a higher cardiac noradrenaline turnover than in WKY rats, may suggest that the cardiac hyperadrenergic activity observed in prehypertensive SHR is maintained, at least in part, by the participation of peripheral, postsynaptic component(s) involving beta 1-adrenergic receptor dysregulation. In addition, the present data suggest that the previously reported evidence of an age-related decrease in cardiac beta 1-adrenergic receptors in rats may be determined at the transcriptional level.

Media: lumen ratio in human small resistance arteries is related to forearm minimal vascular resistance.

BACKGROUND: For the evaluation in humans of structural alterations in resistance arteries, most studies have used an indirect index, the measurement of minimal vascular resistance (mean blood pressure divided by maximal postischaemic blood flow) in suitable vascular beds. A sensitive and specific micromyographic technique was recently made available for the study of human small resistance arteries. Whether a correlation really exists between results obtained with the two techniques has not yet been investigated. OBJECTIVE: To evaluate both forearm minimal vascular resistance and media:lumen ratio of omental or subcutaneous small arteries in normotensive subjects and hypertensive patients. DESIGN AND METHODS: Thirty-four individuals were included in the study (age range 35-74 years; 24 hypertensive, 10 normotensive). Twenty-five had elective abdominal surgery and nine hypertensive patients had a gluteal biopsy. Omental and subcutaneous small arteries were dissected and mounted on a wire micromyograph (Mulvany's technique), and media:lumen ratio and media thickness were measured. The dose-response curve to noradrenaline was constructed at cumulative concentrations from 3 x 10(-9) to 3 x 10(-5) mol/l. Venous occlusion plethysmography was used to measure blood flow in the forearm, and minimal vascular resistance was calculated from mean blood pressure and postischaemic maximal blood flow (13 min ischaemia plus exercise). RESULTS: A statistically significant correlation was found between media:lumen ratio and minimal vascular resistance (r = 0.74, P < 0.001) as well as between media:lumen ratio and systolic (r = 0.44, P < 0.01) and diastolic (r = 0.38, P < 0.05) blood pressures. Similar correlations were observed between media thickness and systolic and diastolic blood pressures. Small arteries from hypertensive patients had a significantly increased reactivity to noradrenaline (by analysis of variance) compared with those from normotensive subjects, in terms of wall tension but not of active media stress. CONCLUSIONS: The present study demonstrated that the media:lumen ratio of small resistance vessels is significantly related to forearm minimal vascular resistance, suggesting that direct and indirect evaluations of vascular morphology will give similar results.

Structural changes of small resistance arteries in spontaneously hypertensive rats after treatment with various doses of lacidipine.

OBJECTIVE: To evaluate the modifications of the morphology of mesenteric small resistance vessels in spontaneously hypertensive rats (SHR) induced by lacidipine treatment. METHODS: Lacidipine was administered at three different dosages, 20, 10, and 0.3 mg/kg per day. Fifty rats were studied. Nine SHR and 11 Wistar-Kyoto (WKY) rats were not treated. Each lacidipine dose was administered to 10 SHR. The drug and the placebo were administered by gavage from age 4 to age 12 weeks. The blood pressure was measured noninvasively every week. The animals were killed when they were aged 13 weeks, and the relative left ventricular mass (left ventricular weight plus septum weight/body weight) was calculated. Small mesenteric resistance vessels were dissected and mounted on a micromyograph (Mulvany's technique), and morphological parameters of the vessels were studied (media thickness and media: lumen ratio). RESULTS: The systolic blood pressure of SHR administered 20 and 10 mg/kg lacidipine per day was reduced significantly during the treatment period, whereas that of rats treated with 0.3 mg/kg lacidipine per day did not change. A significant reduction in media: lumen ratio was observed for all three groups of treated rats, including those to which 0.3 mg/kg lacidipine per day had been administered, and no reduction in systolic blood pressure could be detected. The relative left ventricular mass was reduced significantly only in rats to which 20 and 10 mg/kg lacidipine per day had been administered. CONCLUSION: A significant reduction in magnitude of vascular structural alternations was observed even in SHR treated with a low, nonhypotensive dose of lacidipine.

Relationship between sympathetic nervous system activity, baroreflex and cardiovascular effects after acute nitric oxide synthesis inhibition in humans.

OBJECTIVE: To examine the cardiovascular effects of acute systemic nitric oxide synthesis inhibition in humans in relation to the possible involvement of changes in sympathetic nervous system activity or in the baroreceptor reflex. DESIGN: Placebo or NG-monomethyl-L-arginine (250 mg by intravenous infusion for 5 min) was administered to seven healthy male volunteers according to a random, double-blind sequence. METHODS: Blood pressure and heart rate were measured non-invasively using a Finapres device from 20 min before to 80 min after starting infusion; beat-to-beat variability of blood pressure, pulse interval and systolic blood pressure and pulse interval covariation were assessed by means of spectral and sequence analysis methods. Under basal conditions and 15 min and 60 min after infusion, we measured stroke volume and indices of cardiac systolic and diastolic function by echocardiography, forearm blood flow by strain-gauge venous occlusion plethysmography, and plasma catecholamine levels. RESULTS: Compared with placebo, administration of NG-monomethyl-L-arginine caused a transient increase in blood pressure and reduction in heart rate. Stroke volume and indices of cardiac function did not change significantly, whereas cardiac index and forearm blood flow were significantly reduced after 15 min. Spectral analysis of blood pressure and pulse interval showed a significant reduction of power spectral density in the low frequencies (0.03-0.15 Hz) that persisted 60 min after infusion. The plasma noradrenaline level was significantly reduced after 15 min. No change in baroreflex engagement or sensitivity was detected by the cross-spectral or the sequence method. CONCLUSIONS: Acute systemic nitric oxide synthesis inhibition transiently increases blood pressure and reduces heart rate and cardiac index. The acute hypertensive response to NG-monomethyl-L-arginine is dependent neither on sympathetic nervous system activity, which is probably reduced as a consequence of baroreceptor reflex activation, nor on baroreceptor reflex sensitivity, which is not impaired.

Arterial spontaneous rhythmic contractile activity in humans and rats: spectral analysis and regulatory mechanisms.

OBJECTIVE: Many experimental observations have demonstrated the presence of spontaneous cyclic vasomotor activity (CVA) in large and small arteries. This study aimed to evaluate the characteristics of spontaneous CVA in rat and human resistance arteries, and to investigate its possible interference with the evaluation of sympathetic activity by means of spectral analysis of blood pressure in vivo. DESIGN AND RESULTS: In study 1 we examined small mesenteric arteries of spontaneously hypertensive rats and Wistar-Kyoto rats, as well as small omental arteries of normotensive subjects and hypertensive patients (Mulvany and Halpern technique). CVA was enhanced by the agonists of nitric oxide release, and was abolished by the inhibitors of nitric oxide or cyclic GMP synthesis. A potassium channel, which is barium- and zinc-sensitive and tetraethylammonium-insensitive, seems to play a crucial role in the genesis of CVA. In rats and in humans the frequency of CVA fell exactly in the frequency band ('low frequencies') of power spectral analysis of blood pressure usually considered to be an 'index of sympathetic activity'. In study 2, a power spectral analysis of blood pressure variability before and after intra-arterial infusion of noradrenaline or acetylcholine was performed in 18 patients with mild-to-moderate hypertension. The absolute and normalized spectral power of the low-frequency systolic blood pressure peak increased remarkably after noradrenaline and acetylcholine infusion, while its central frequency shifted from 0.10 Hz to approximately 0.06 Hz, exactly the frequency of CVA observed in vitro. CONCLUSIONS: A potassium channel appears to be involved in the genesis of CVA. Also, CVA might contribute to the blood pressure variability independently of the autonomic nervous system activity, and thus probably plays a role in the genesis of the low-frequency peak in the rat and in humans.

Effects of antihypertensive therapy with angiotensin converting enzyme inhibitors or calcium antagonists on spontaneous cyclic vasomotor activity in small resistance arteries of spontaneously hypertensive rats.

OBJECTIVE: Spontaneous cyclic vasomotor activity can occur in small resistance arteries in vitro after precontraction with a vasoconstrictor. Calcium and potassium channels and nitric oxide synthesis or release seem to be involved in the genesis of this vasomotor activity. We therefore investigated the effects of chronic antihypertensive therapy with calcium antagonists and angiotensin converting enzyme (ACE) inhibitors on the amplitude and frequency of cyclic vasomotor activity in vitro in spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: SHR were treated with fosinopril at 25 mg/kg per day or lacidipine at 10 mg/kg per day or nitrendipine at 30 mg/kg per day, from the age of 4 to 12 weeks. Data were compared with those obtained in untreated SHR and Wistar-Kyoto (WKY) rats. Half the rats were killed at 13 weeks of age, and the remaining half were killed at 38 weeks of age. The mesenteric small resistance arteries were dissected, mounted on a micromyograph and then contracted submaximally with noradrenaline. Acetylcholine was then added to the organ bath. RESULTS: More than 50% of the vessels showed cyclic vasomotor activity. The frequency and amplitude of this activity were greater in SHR than WKY rats after noradrenaline and after acetylcholine. At 13 weeks of age (but not at 38 weeks of age), treatment with a calcium antagonist (either lacidipine or nitrendipine) significantly reduced the frequency and amplitude of the vasomotor activity, probably by interfering with calcium entry. No change was observed after fosinopril. CONCLUSIONS: Antihypertensive treatment with different drugs may affect cyclic vasomotor activity differently, probably by interfering with cellular mechanisms involved in its genesis. The effects of calcium antagonists on cyclic vasomotor activity are still present after short-term but not after long-term treatment withdrawal.

Effects of long-term antihypertensive treatment with lisinopril on resistance arteries in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE: To evaluate the effects of long-term antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril on structural alterations and the endothelial function of small resistance arteries in hypertensive patients with left ventricular hypertrophy. METHODS: Fourteen patients with left ventricular hypertrophy were treated for 3 years with a lisinopril-based regimen. Patients underwent an echocardiographic evaluation of left ventricular mass index at baseline, during the first and third years of treatment. At the end of the treatment period, subcutaneous small resistance arteries (obtained by biopsy of the subcutaneous fat from the gluteal region) were dissected and mounted on a micromyograph (Mulvany's technique); the media : lumen ratio was then calculated. Data obtained were compared with those observed for 14 untreated essential hypertensive patients and 14 normotensive subjects, age- and sex-matched. RESULTS: In the present study, a significantly lower media : lumen ratio was observed in treated compared with untreated hypertensive patients, although it remained significantly higher than that in normotensive subjects. In treated hypertensive patients a significant reduction in clinic blood pressure was observed. However, their blood pressure remained significantly higher than that in normotensive subjects. Significant correlations between the media : lumen ratio and blood pressure, left ventricular mass index or changes in left ventricular mass index during treatment were observed. The response to acetylcholine administration was reduced in untreated hypertensives compared with that in normotensives. In patients treated with lisinopril, the vasodilatation obtained with the two higher doses of acetylcholine was greater than that in untreated hypertensives, thus suggesting an improvement of endothelial function. CONCLUSIONS: Long-term therapy based on lisinopril was associated with a smaller media : lumen ratio in the subcutaneous small resistance arteries of hypertensive patients with left ventricular hypertrophy. Our retrospective study confirms previous findings obtained in prospective studies with other angiotensin converting enzyme inhibitors. Endothelial function was probably improved by lisinopril therapy.

Structural association between the carotid artery and the left ventricle in a general population in Northern Italy: the Vobarno study.

OBJECTIVE: To evaluate the interrelationships between structural alterations in the carotid arteries and left ventricular geometric patterns in a middle-aged general population. DESIGN AND METHODS: We studied 223 untreated subjects (106 females, 117 males; aged 48-64 years) living in a small town in Northern Italy (Vobarno, Brescia), using a cross-sectional design. The left ventricular mass index was assessed by echocardiography, while the intima-media thickness and the occurrence of plaque were evaluated by ultrasound. Blood pressure was determined by clinic measurements and by 24 h noninvasive ambulatory blood pressure monitoring. RESULTS: According to the presence of left ventricular hypertrophy (left ventricular mass index > 50 g/m2.7 in males and > 47 g/m2.7 in females) or concentric left ventricular remodelling (normal left ventricular mass index and relative wall thickness > 0.42), the subjects were divided into four groups: 124 subjects with normal left ventricular geometry, 73 subjects with left ventricular hypertrophy (55 with eccentric and 18 with concentric hypertrophy) and 26 subjects with concentric remodelling. The common carotid intima-media thickness and cross-sectional area were significantly greater in the subjects with concentric left ventricular hypertrophy (analysis of variance, P< 0.05) than in those with normal left ventricular geometry. A significantly higher number of plaques was observed in subjects with concentric and eccentric left ventricular hypertrophy. CONCLUSIONS: In a general population of unselected middle-aged subjects, the presence of concentric left ventricular hypertrophy was associated with an increase in intima-media thickness and with the presence of plaque in the carotid arteries, possibly contributing to the worse prognosis observed in this group of patients.