Antimicrobial efficacy and inactivation kinetics of a novel LED-based UV-irradiation technology.

BACKGROUND: Ultraviolet (UV)-light-emitting diodes (UV-LEDs) are energy efficient and of special interest for the inactivation of micro-organisms. In the context of the coronavirus disease 2019 pandemic, novel UV technologies can offer a powerful alternative for effective infection prevention and control. METHODS: This study assessed the antimicrobial efficacy of UV-C LEDs on Escherichia coli, Pseudomonas fluorescens and Listeria innocua, as well as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), human immunodeficiency virus-1 (HIV-1) and murine norovirus (MNV), dried on inanimate surfaces, based on European Standard EN 17272. RESULTS: This study found 90% inactivation rates for the tested bacteria at mean UV-C doses, averaged over all three investigated UV-C wavelengths, of 1.7 mJ/cm2 for E. coli, 1.9 mJ/cm2 for P. fluorescens and 1.5 mJ/cm2 for L. innocua. For the tested viruses, UV doses <15 mJ/cm2 resulted in 90% inactivation at wavelengths of 255 and 265 nm. Exposure of viruses to longer UV wavelengths, such as 275 and 285 nm, required much higher doses (up to 120 mJ/cm2) for inactivation. Regarding inactivation, non-enveloped MNV required much higher UV doses for all tested wavelengths compared with SARS-CoV-2 or HIV-1. CONCLUSION: Overall, the results support the use of LEDs emitting at shorter wavelengths of the UV-C spectrum to inactivate bacteria as well as enveloped and non-enveloped viruses by exposure to the appropriate UV dose. However, low availability and excessive production costs of shortwave UV-C LEDs restricts implementation at present, and supports the use of longwave UV-C LEDs in combination with higher irradiation doses.

Formation of even-numbered hydrogen cluster cations in ultracold helium droplets.

Neutral hydrogen clusters are grown in ultracold helium nanodroplets by successive pickup of hydrogen molecules. Even-numbered hydrogen cluster cations are observed upon electron-impact ionization with and without attached helium atoms and in addition to the familiar odd-numbered H(n)(+). The helium matrix affects the fragmentation dynamics that usually lead to the formation of overwhelmingly odd-numbered H(n)(+). The use of high-resolution mass spectrometry allows the unambiguous identification of even-numbered H(n)(+) up to n approximately = 120 by their mass excess that distinguishes them from He(n)(+), mixed He(m)H(n)(+), and background ions. The large range in size of these hydrogen cluster ions is unprecedented, as is the accuracy of their definition. Apart from the previously observed magic number n=6, pronounced drops in the abundance of even-numbered cluster ions are seen at n=30 and 114, which suggest icosahedral shell closures at H(6)(+)(H(2))(12) and H(6)(+)(H(2))(54). Possible isomers of H(6)(+) are identified at the quadratic configuration interaction with inclusion of single and double excitations (QCISD)/aug-cc-pVTZ level of theory.

Severely impaired baroreflex-buffering in patients with monogenic hypertension and neurovascular contact.

BACKGROUND: We identified a family with a monogenic syndrome of hypertension, brachydactyly, and neurovascular contact of the brain stem. Neurovascular contact of the ventrolateral medulla may lead to arterial hypertension by interfering with baroreflex function. METHODS AND RESULTS: In 5 patients with monogenic hypertension (18 to 34 years old), we conducted detailed autonomic function tests. Blood pressure during complete ganglionic blockade was 134+/-4.9/82+/-4.1 mm Hg and 90+/-6/49+/-2.4 mm Hg in patients and in control subjects, respectively. During ganglionic blockade, plasma vasopressin concentration increased 24-fold in control subjects and <2-fold in patients. In patients, cold pressor testing, hand-grip testing, and upright posture all increased blood pressure excessively. In contrast, muscle sympathetic nerve activity was not increased at rest or during cold pressor testing. The phenylephrine dose that increased systolic blood pressure 12.5 mm Hg was 8.0+/-2.0 microg in patients and 135+/-35 microg in control subjects before ganglionic blockade and 5.4+/-0.4 microg in patients and 13+/-4.8 microg in control subjects during ganglionic blockade. CONCLUSIONS: In patients with monogenic hypertension and neurovascular contact, basal blood pressure was increased even during sympathetic and parasympathetic nerve traffic interruption. However, sympathetic stimuli caused an excessive increase in blood pressure. This excessive response cannot be explained by increased sympathetic nerve traffic or increased vascular sensitivity. Instead, we suggest that baroreflex buffering and baroreflex-mediated vasopressin release are severely impaired.

Central blood volume: a determinant of early cardiac adaptation in arterial hypertension?

OBJECTIVES: This study was undertaken to assess the influence of the fluid volume state on cardiac adaptation to hypertension. BACKGROUND: Left ventricular hypertrophy is an important predictor of hypertensive complications. We analyzed volume status and its impact on cardiac structural changes in early hypertension. METHODS: In 33 normotensive subjects, 40 patients with borderline hypertension and 63 patients with established essential hypertension, mean arterial pressure was measured invasively; total blood volume was measured by iodine-125-labeled plasma albumin and hematocrit; central blood volume by indocyanine green dye dilution curve; and diastolic diameter and left ventricular mass by two-dimensional-guided M-mode echocardiography. RESULTS: Central blood volume was approximately 20% higher in patients with stage I borderline hypertension than in normotensive subjects ([mean +/- SD] 3,001 +/- 663 vs. 2,493 +/- 542 ml, p < 0.05), whereas total blood volume was similar in all three groups. This shift in intravascular volume toward the cardiopulmonary circulation was accompanied by a significant increase in diastolic diameter (5.29 +/- 0.80 vs. 4.86 +/- 0.77 cm, p < 0.05) and in left ventricular mass (239.4 +/- 90.6 vs. 183.5 +/- 68.8 g, p < 0.05) in patients with borderline hypertension compared with subjects with normotension. In patients with established essential hypertension, volume status of stroke volume and diastolic dimension returned to normal values, whereas left ventricular mass increased further. CONCLUSIONS: We conclude that the early phase of hypertension is characterized by centripetal distribution of intravascular volume, leading to an increased preload to the left ventricle. This change in volume status appears to be related to cardiac structural adaptation to an increase in arterial pressure.

Long-term results after microvascular decompression in essential hypertension.

BACKGROUND AND PURPOSE: In 1998, 8 patients with severe, intractable arterial hypertension and MR tomography-demonstrated neurovascular contact of a looping artery at the root entry zone of cranial nerves IX and X, causing neurovascular compression, underwent neurosurgical decompression. The short-term results showed a normalization of blood pressure with a markedly reduced antihypertensive drug regimen in 7 patients. To determine the longer-term outcome concerning blood pressure and secondary organ damage after neurovascular decompression, we studied these 8 operated patients prospectively for a mean follow-up of 3.5 years after surgical intervention. METHODS: Eight hypertensive patients who had undergone microsurgical decompression were monitored every 6 months after surgery to assess blood pressure (by 24-hour ambulatory pressure readings) and the need for antihypertensive medication. To evaluate secondary organ damage, echocardiographic assessment of left ventricular hypertrophy, fundoscopic assessment of hypertensive lesions, and analysis of renal function and proteinuria were done. RESULTS: Three of the 8 operated patients remained normotensive in the long-term period with decreased antihypertensive medication. Two patients required gradual increases of antihypertensive medication after the first postoperative year, after which arterial blood pressure levels were 10% to 15% lower than preoperative levels. Three patients suffered serious cardiovascular and renal complications, with the incidence of lethal intracerebral hemorrhage in 1 patient and end-stage renal disease in 2 patients, of whom 1 experienced sudden cardiac death. CONCLUSIONS: The long-term results verify that microsurgical decompression is a successful alternative therapy in a certain subgroup of patients with arterial hypertension due to neurovascular compression. However, the relevance of the looping artery in the other cases, who did not improve, is not clear. Prospective studies to elucidate the pathophysiological role of neurovascular abnormalities and arterial hypertension are needed.

Effects of bromocriptine on cardiovascular regulation in healthy humans.

Bromocriptine, a dopamine agonist with central nervous system actions, may reduce sympathetic nervous system activity. We tested this hypothesis by measuring arterial blood pressure, central venous pressure, heart rate, muscle sympathetic nerve activity, and forearm blood flow before and after unloading the arterial baroreceptors with sodium nitroprusside (0.5 to 1.5 mcg/kg per minute IV), before and after unloading the cardiopulmonary baroreceptors with incremental lower body negative pressure (0 to -15 mm Hg), and before and after immersion of the hand in ice-cold water for 2 minutes (cold pressor test). After obtaining basal responses to provocative maneuvers, we gave 20 healthy subjects either 5 mg oral bromocriptine (n = 10) or placebo (n = 10) in a randomized, double-blind fashion. Bromocriptine did not affect resting mean arterial pressure, heart rate, or forearm blood flow. Bromocriptine decreased resting central venous pressure by 1.2 mm Hg (P < .05) and tended to increase total integrated muscle sympathetic nerve activity (from 151 +/- 44 to 212 +/- 82 U/min, P = NS). The reflex increases in muscle sympathetic nerve activity to nitroprusside infusion and lower body negative pressure were unchanged by bromocriptine; however, vascular responsiveness to both maneuvers was impaired after bromocriptine administration compared with control. Without bromocriptine, the reflex increase in muscle sympathetic nerve activity after nitroprusside-induced hypotension maintained forearm blood flow at a constant level, whereas with bromocriptine the forearm blood flow increased from 1.9 +/- 0.3 to 2.8 +/- 0.6 mL/min per 100 mL (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of digitalis on chemoreflex responses in humans.

To investigate the effects of digitalis on chemoreflexes in humans, we measured muscle sympathetic nerve activity (microneurography), minute ventilation, oxygen saturation, end-tidal carbon dioxide, mean arterial pressure, heart rate, and central venous pressure during stimulation of peripheral chemoreceptors with hypoxia, during stimulation of central chemoreceptors with hypercapnia, and during a cold pressor test before and after digitalis and placebo in 10 healthy volunteers on two different days (randomized, double-blind, cross-over design). Digitalis did not affect baseline measurements significantly. Despite similar changes in oxygen saturation and end-tidal carbon dioxide during hypoxia and hypercapnia with both placebo and digitalis, digitalis significantly potentiated overall ventilatory responses to hypoxia (+67 +/- 12% before versus +98 +/- 3% after digitalis; mean +/- SEM; P < .01) but did not affect the response to hypercapnia. Sympathetic nerve activity increased by 25 +/- 9% during hypoxia before digitalis and 30 +/- 10% during hypoxia after digitalis (P = NS) and increased by 38 +/- 18% during hypercapnia before digitalis and 26 +/- 11% during hypercapnia after digitalis (P = NS). Digitalis did not significantly change responses to the cold pressor test. Placebo had no effect on ventilatory and sympathetic nerve activity responses. We conclude that digitalis selectively augments ventilatory responses to peripheral chemoreceptor stimulation by hypoxia.

Hemodynamic and sympathetic nerve responses to painful stimuli in normotensive and borderline hypertensive subjects.

Observations in animals and humans show that pain sensitivity might be lower (and pain tolerance higher) in hypertensive as compared to normotensive subjects. One hypothesis, derived from experimental studies, assumes that enhanced activation of baroreceptors leads to an enhanced central inhibition. A central hypothesis assumes changes in the central (endogenous) control of the nociceptive system. To investigate these two hypotheses we quantitatively assessed the minute-by-minute changes in mean arterial pressure (MAP), central venous pressure (CVP) heart rate (HR), muscle sympathetic nerve activity (MSNA), and individual pain ratings during noxious mechanostimulation in 10 normotensive (NT) and 13 borderline hypertensive (BH) subjects. Linear regression analysis indicated a close negative correlation for the overall data between resting levels of MAP and pain ratings (r = -0.57, P < 0.0001). The BH group exhibited a lower pain sensitivity compared to the NT group (P < 0.001). The extent of baroreceptor activation during the application of pain was not different between the two groups (P = NS) as assessed by almost identical increases in MAP (+8 +/- 1 vs. +9 +/- 1 mmHg NT vs. BH group), CVP (+0.7 +/- 0.1 vs. +0.5 +/- 0.1 mmHg), HR (+2 +/- 1 vs. +2 +/- 1 beats/min), and MSNA (+5 +/- 1 +4 +/- 1 bursts/min). The NT subjects exhibited significant correlations between the pain ratings and the increases in MAP (r = +0.52; P < 0.05) and MSNA (r = +0.49; P < 0.05) whereas the BH subjects did not show such a relationship. Thus, the increased pain tolerance in human hypertension cannot be explained by hemodynamically mediated differences in the activation of baroreceptors or by an altered baroreflex sensitivity during the application of pain. We conclude, that the reduced pain sensitivity in hypertensive humans is more likely related to central changes.

Hyper-responsiveness to angiotensin II is related to cardiac structural adaptation in hypertensive subjects.

BACKGROUND: Angiotensin II has been found to be a growth stimulating factor for myocardial cells. In humans, angiotensin II infusion causes vasoconstriction in systemic and renal vasculature and leads to aldosterone secretion. Our hypothesis was that hyper-responsiveness to angiotensin II is related to left ventricular mass in human essential hypertension. METHODS AND RESULTS: In 30 normotensive individuals and 30 subjects with mild essential hypertension (white men, mean age 26+/-3 years), the responsiveness to angiotensin II was assessed by measuring changes in mean arterial pressure, renal blood flow, glomerular filtration rate and aldosterone secretion in response to i.v. angiotensin II infusion (0.5 and 3.0 ng/kg per min). The provoked changes to angiotensin II infusion were similar in the normotensive and hypertensive group with the exception of an exaggerated increase in mean arterial pressure in hypertensives (14+/-5 versus 10+/-5 mm Hg, P<0.001 at 3.0 ng/kg per min angiotensin II). The increase in mean arterial pressure was correlated with left ventricular mass in hypertensive subjects (angiotensin II 0.5 ng/kg per min: r = 0.49, P<0.005; angiotensin II 3.0 ng/kg per min: r = 0.35, P<0.05); no such correlation was found in the normotensive group. After taking into account baseline mean arterial pressure and body mass index, the increase in mean arterial pressure to angiotensin II 0.5 ng/kg per min was still correlated with left ventricular mass (partial r = 0.50, P<0.01). Similarly, the change of glomerular filtration rate but not of renal blood flow in response to angiotensin II 0.5 ng/kg per min was correlated with left ventricular mass, (r = 0.42, P<0.02) in the hypertensive group but not in the normotensive one. This relationship remained significant even after taking baseline glomerular filtration rate, mean arterial pressure and body mass index into account (partial r = 0.43, P<0.05). CONCLUSION: Hyper-responsiveness to angiotensin II is related to an increased left ventricular mass in hypertensive subjects independent of blood pressure.

Effects of angiotensin converting enzyme inhibitor on renal haemodynamics during mental stress.

OBJECTIVE: To examine the effects of angiotensin converting enzyme (ACE) inhibition on renal and systemic haemodynamics as well as on humoral regulators, under resting conditions and during mental stress in 20 normotensive and 20 mildly hypertensive subjects. METHODS: All of the subjects received either 25 mg cilazapril or placebo once a day, in a randomized, double-blind, cross-over trial for 1 week, followed by a 2-week washout period before the alternative regimen was given. We measured renal blood flow with para-aminohippuran, glomerular filtration rate with inulin, cardiac output by impedance cardiography and blood pressure and heart rate by an oscillometric method. We also monitored effects on plasma renin activity, aldosterone, catecholamines and atrial natriuretic peptide. Mental stress consisted of a long-lasting, time-reaction device, thereby provoking activation of the sympathetic nervous system. RESULTS: At rest ACE inhibition lowered mean arterial pressure (92 +/- 10 versus 98 +/- 9 mmHg), increased renal blood flow (803 +/- 109 versus 707 +/- 93 ml/min) and the renal fraction of cardiac output (25.9 +/- 2.5 versus 23.5 +/- 2.5%) and decreased the filtration fraction (17.9 +/- 2.5 versus 19.8 +/- 2.7%) in hypertensive but not in normotensive subjects. Sympathetic activation by mental stress leading to a transient increase in blood pressure did not alter significantly the effects of ACE inhibition on renal and systemic haemodynamics, in normotensive or in hypertensive subjects, although a tendency towards attenuation of the rise in glomerular filtration rate was noted in hypertensives (7.2 +/- 1.0 versus 5.1 +/- 0.8%). ACE inhibition led to increased plasma noradrenaline at rest but not during mental stress in hypertensive patients. CONCLUSION: ACE inhibition in patients with mild hypertension increased selectively renal perfusion, which is conserved during mental stress without persistent effects on the sympathetic nervous system. Thus, mental stress as a correlate of daily life stress appeared not to confound the selective renal vasodilatory effect of ACE inhibitors.

Normalization of circadian blood pressure profiles after renal transplantation.

Most patients with secondary hypertension due to renal disease or on maintenance hemodialysis have lost the physiologic fall of blood pressure during sleep. To test the notion that kidney transplantation normalizes the blood pressure profile, we monitored ambulatory blood pressure over 24 hr in 45 patients (29 males and 16 females) after successful renal transplantation. The longer the time after renal transplantation, the more marked was the decrease of blood pressure during sleep (r = 0.38, P < 0.01). This effect of time after renal transplantation on the fall of blood pressure during sleep was independent of the prevailing level of 24-hr ambulatory blood pressure. The prevalence of dippers (defined by a fall in mean blood pressure during sleep of 10% or more of the awake mean) increased from 27% in the early phase (< 7 months) to 73% in the late phase (> or = 1 year) after renal transplantation (P < 0.01). Again, this effect was not attributable to the level of 24-hr ambulatory blood pressure and concomitant antihypertensive or immunosuppressive medication. We conclude that renal transplantation leads to a normalization of the circadian blood pressure profile with a marked decrease of blood pressure during sleep. As a consequence, the lower hemodynamic load imposed on the cardiovascular system may in turn lead to a reduction of cardiovascular morbidity and mortality.

Is endothelial dysfunction reversible?

To date, the published database concerning the impact of therapy on endothelial function in essential hypertension and hypercholesterolemia is small and incomplete. Chronic antihypertensive therapy had not yet been proven to restore endothelial function in patients with essential hypertension. In contrast, chronic lipid-lowering therapy is effective in restoring endothelial function of the coronary and peripheral circulation in patients with hypercholesterolemia. A beneficial effect was already documented after 3 months of therapy with fluvastatin but full restoration may last more than 1 year.

Impact of aldosterone on left ventricular structure and function in young normotensive and mildly hypertensive subjects.

Left ventricular (LV) hypertrophy is an independent risk factor for cardiovascular morbidity and mortality. Experimental data revealed that elevated circulating aldosterone is associated with increased collagen accumulation resulting in myocardial fibrosis. To analyze whether aldosterone is also associated with cardiac structural and functional changes in humans, we examined the effects of aldosterone on LV structure and function before and after suppression of aldosterone by increasing oral salt intake. The study group comprised 26 normotensive male white healthy control subjects (age 26 +/- 3 years) and 31 male white subjects (age 25 +/- 3 years) with mild essential hypertension (World Health Organization stages I to II). Two-dimensional-guided M-mode echocardiography and 24-hour ambulatory blood pressure (BP) monitoring was performed in each subject. Simultaneously, we measured 24-hour urinary sodium excretion, 24-hour urinary aldosterone, and serum aldosterone concentration at baseline and after increasing oral salt intake to suppress aldosterone secretion. In all subjects LV mass correlated with body mass index (r = 0.42, p <0.001) and both 24-hour ambulatory systolic (r = 0.28, p <0.05) and diastolic (r = 0.25, p <0.05) BP. Changes in urinary sodium excretion correlated inversely with changes in serum aldosterone concentration (r = -0.28; p <0.05). Urinary aldosterone concentration after salt loading decreased in normotensive (10.98 vs 7.44 microg/24 hours; p <0.02) but not in hypertensive (9.34 vs 10.51 microg/24 hours; p = NS) subjects. Serum and urinary aldosterone levels at baseline were not related to LV structure or function. In contrast, after increasing oral salt intake, urinary aldosterone concentration was related to LV mass (r = 0.43; p <0.01) and impaired midwall fractional fiber shortening (r = -0.33; p <0.02) in all subjects, independent of 24-hour ambulatory BP. Subgroup analysis revealed that this was significant only in hypertensive (r = 0.46; p <0.01 and r = -0.44; p <0.02, respectively) but not in normotensive (r = 0.28 and -0.16; p = NS for both, respectively) subjects. Consistently, the greater serum aldosterone remained after increasing oral salt intake, the greater was LV mass (r = 0.35; p <0.01). The latter was found in hypertensive subjects (r = 0.44; p <0.02), independent of 24-hour ambulatory BP, but not in normotensive subjects (r = 0.025; p = NS). Inadequate suppression of aldosterone in response to an increase in oral salt intake is related to LV structural and functional changes in hypertensive subjects. Thus, our results support experimental data indicating that aldosterone affects LV structure and function in humans and that this effect is BP independent.

Sympathetic responses of patients with congestive heart failure to cold pressor stimulus.

Studies in patients with congestive heart failure (CHF) demonstrate blunting of sympathoexcitatory responses to baroreflex perturbation. Whereas experimental and limited clinical evidence suggests impairment of baroreflex mechanisms as the etiology of these attenuated responses, an alternative mechanism would be an inability of patients with CHF to increase sympathetic neural outflow above markedly elevated baseline levels. Hemodynamic and sympathetic neural responses (peroneal microneurography) were therefore compared of normal subjects (n = 10) and patients with CHF (n = 10) during the non-baroreflex sympathoexcitatory stimulus of the cold pressor test. The cold pressor stimulus produced increases in arterial pressure and heart rate in both groups. During hand immersion in ice water, normal subjects demonstrated significant increases in muscle sympathetic nerve activity expressed as burst frequency (20 +/- 2 to 28 +/- 3 bursts/min, p less than 0.01), total integrated nerve activity (224 +/- 41 to 342 +/- 62 U/min, p less than 0.05), and total activity corrected for accompanying changes in heart rate (375 +/- 81 to 538 +/- 118 U/100 heart beats, p less than 0.05). Similarly, despite elevated control levels of sympathetic activity, patients with CHF also demonstrated significant sympathoexcitatory responses to the cold pressor stimulus, with increases in muscle sympathetic nerve burst frequency (60 +/- 7 to 67 +/- 7 bursts/min, p less than 0.01) total integrated nerve activity (818 +/- 159 to 1,015 +/- 191 U, p less than 0.001), and total activity corrected for accompanying changes in heart rate (1,008 +/- 178 to 1,173 +/- 201 U/100 heart beats, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Is endothelial function of the radial artery altered in human essential hypertension?

There is controversy over whether endothelial function is impaired in human essential hypertension. All studies to date have used measurements of forearm blood flow by plethysmography to assess endothelium-dependent vasodilation and endothelial function. In contrast to these studies, which have focused on resistance vessels, we have determined what effects the endothelium has on underlying smooth muscle cells in conduit arteries by measuring arterial compliance of the radial arteries (change in diameter of radial artery over pressure for each arterial pulse). In 13 normotensive healthy subjects and 11 young patients with essential hypertension, arterial compliance of the radial artery was assessed directly with a new high-precision ultrasonic device (NIUS 02) after infusion of acetylcholine (endothelium-dependent response) or sodium nitroprusside (endothelium-independent response). Arterial compliance of the radial artery was similar at baseline and with increasing doses of acetylcholine and sodium nitroprusside in normotensive and in hypertensive subjects. The increase in arterial compliance from baseline at each individual concentration of acetylcholine and sodium nitroprusside was the same in both normotensive and hypertensive subjects. However, after a single oral dose of a combination of the angiotensin converting enzyme inhibitor spirapril and the calcium entry blocker isradipine, the increase in arterial compliance in response to the maximum dose of intraarterial acetylcholine was enhanced in normotensives (0.38 +/- 1.23 to 0.76 +/- 1.01 mm2/mm Hg x 10(-3), P < .05), but not in hypertensives (+0.41 +/- 1.26 to 0.36 +/- 1.31 mm2/mm Hg x 10(-3), not significant), and differed significantly between normotensive and hypertensive subjects (P < .05). Thus, pharmacologic stimulation disclosed a blunted response of endothelium-dependent action in the arterial compliance of the conduit arteries in hypertensive subjects. This suggests an impaired endothelial function reserve in persons with essential hypertension.

Angiotensin II stimulates left ventricular hypertrophy in hypertensive patients independently of blood pressure.

Angiotensin II (AII) is known to be a growth stimulating factor for myocardial cells. We examined whether an exaggerated responsiveness to AII might aggravate left ventricular (LV) hypertrophy in human essential hypertension. To determine the responsiveness to AII in humans, we examined changes in mean arterial pressure (MAP), renal blood flow (RBF), and glomerular filtration rate (GFR) (steady state input clearance technique with para-aminohippurate and inulin, respectively) and aldosterone secretion to AII infusions (0.5 and 3.0 ng/kg/min) in 71 normotensive male and 48 hypertensive male subjects (age: 26 +/- 3 years; 24-h ambulatory blood pressure: 121 +/- 5/71 +/- 4 mmHg v 138 +/- 7/82 +/- 7 mmHg, P < .001). In addition, each patient underwent two-dimensional guided M-mode echocardiography at rest to assess cardiac structure and function. When given AII 3.0, a greater increase of MAP (13 +/- 7 v 17 +/- 8 mm Hg, P < .022) and a more marked decrease of RBF (-203 +/- 123 mL/min v -270 +/- 137 mL/min, P < .007) were found in hypertensives than in normotensives, whereas changes in GFR and aldosterone concentration were similar in both groups. Most important, changes in GFR to AII correlated with echocardiographically determined LV mass (normotensives: AII 0.5: r = 0.33, P < .006, AII 3.0: r = 0.28, P < .05; hypertensives: AII 0.5: r = 0.41, P < .006, AII 3.0: r = 0.32, P < .05). After taking baseline MAP and body mass index into account, the increase in GFR to AII 0.5 in hypertensives still correlated with LV mass (partial r = 0.37, P < .01). Inasmuch as the increase of GFR is a marker of the responsiveness to AII (related to vasoconstriction at the postglomerular site), our data suggest that increased sensitivity to AII is linked to LV hypertrophy in early essential hypertension, independently of the level of blood pressure.

Impact of alpha- versus beta-blockers on hypertensive target organ damage: results of a double-blind, randomized, controlled clinical trial.

In hypertensive disease, the extent of target organ damage determines the prognosis. We conducted a 6-month, double-blind randomized study to compare the effects of an alpha1-adrenoreceptor blocker (bunazosin) with those of a beta1-adrenoreceptor blocker (metoprolol) on early hypertensive target organ damage at a similar level of blood pressure reduction. The study consisted of 43 patients (29 men and 14 women) of varying ages (mean age 52 +/- 9 years) with essential hypertension World Health Organization stage I-II. Both the alpha- and the beta-blocker lowered blood pressure to a similar extent measured by 24-h blood pressure monitoring. The left ventricular mass was comparably reduced in both cohorts (alpha-blocker 284 +/- 80 v 259 +/- 67 g, P < .05, beta-blocker 282 +/- 74 v 254 +/- 70 g, P < .05). Treatment with the alpha-blocker led to reduced total peripheral resistance (22.9 +/- 8.0 v 19.9 +/- 5.3 U, P < .05), whereas therapy with the beta-blocker resulted in an elevated total peripheral resistance (25.5 +/- 8.4 v 28.5 +/- 9.3 U, P < .10; P < .05 for the difference in both groups). Renal plasma flow remained constant in the alpha-blocker treated group but decreased in the beta-blocker treated group (508 +/- 141 v 477 +/- 134 mL/min/1.73 m2, P < .05). Glomerular filtration rate as measured by inulin clearance tended to increase after treatment with the alpha-blocker (112 +/- 20 v 115 +/- 18 mL/min/1.73 m2, P < .10) in accordance with a decrease of serum creatinine (1.00 +/- 0.14 v 0.93 +/- 0.12 mg/dL, P < .001). Plasma cholesterol and LDL cholesterol was lowered after treatment with the alpha-blocker (238 +/- 48 v 312 +/- 37 mg/dL; P < .001, and 153 +/- 32 v 130 +/- 25 mg/dL; P < .05) while remaining unchanged in group treated with the beta-blocker. Left ventricular hypertrophy was similarily reduced with alpha- and with beta-blockade at a comparable reduction of 24-h blood pressure. Alpha-blockers effected a more favorable renal and systemic hemodynamic profile than beta-blockers, but only long-term prospective studies will answer the question whether these hemodynamic effects result into a better cardiovascular prognosis.

Importance of left atrial baroreceptors in the cardiopulmonary baroreflex of normal humans.

In animals, sympathetic responses to orthostasis are regulated in part by cardiopulmonary afferents arising from atrial and ventricular baroreceptors. To determine the relative importance of these baroreceptor regions in the cardiopulmonary baroreflex of normal humans, simultaneous measurements of left atrial and right and left ventricular volumes (cine computed tomography), invasive hemodynamics, forearm vascular resistance (plethysmography), and efferent sympathetic nerve activity to muscle (microneurography) were obtained under control conditions and with nonhypotensive lower body negative pressure (-10 mmHg, LBNP-10) in nine normal human subjects. LBNP-10 did not alter heart rate or mean systemic arterial pressure, but it did produce significant decreases in pulmonary artery diastolic and right atrial pressures. This reduction in cardiac filling pressures resulted in efferent sympathoexcitation evidenced by increases in forearm vascular resistance and efferent sympathetic nerve activity to the muscle. LBNP-10 did not alter end-diastolic volume of the left or the right ventricle. Similarly, ventricular stroke volume was unchanged during LBNP-10, as assessed by cine computed tomography or thermodilution techniques. In contrast, LBNP-10 resulted in a significant decrease in left atrial volume. Thus, LBNP produced a significant decrease in cardiac filling pressures and left atrial volumes with resultant reflex sympathoexcitation, whereas ventricular volumes were unchanged. These observations suggest an important role for left atrial (nonventricular) baroreceptor afferents in the cardiopulmonary baroreflex of normal humans.

Ratio of serum aldosterone to plasma renin concentration in essential hypertension and primary aldosteronism.

The ratio of serum aldosterone to plasma renin activity (PRA) has been proposed as sensitive screening method in the diagnosis of primary aldosteronism under random conditions. However, the method for determination of renin activity is hampered by the necessity of ice cooling during storage and transport. The present study was therefore conducted to examine the ratio of serum aldosterone to plasma renin concentration (ARR) and its usefulness in diagnosis of primary aldosteronism under ambulatory conditions and given antihypertensive medication. 146 patients with arterial hypertension who consecutively attended the outpatient clinic were studied prospectively. Patients with secondary hypertension besides primary aldosteronism were not included in the series. 37 normotensive patients served as control. Also, 17 patients with known primary aldosteronism were retrospectively examined. Among the hypertensive group 2 patients with Conn's syndrome were newly detected (1.4%). ARR was 7.92 +/- 6.04 [pg/ml]/[pg/ml] in normotensive controls (range from 2.03 to 26.98), 14.61 +/- 18.50 [pg/ml]/[pg/ml] in patients with essential hypertension (n = 144, range from 0.41 to 115.45) and 155.92 +/- 127.84 [pg/ml]/[pg/ml] in patients with primary aldosteronism (n = 19, range from 6.75 to 515). 17 of the 19 patients with Conn's syndrome had an ARR of more than 50. Under ongoing drug treatment this represents a sensitivity of 89% and a specificity of 96%. Sensitivity decreased to 84% and specificity increased to 100% when a second criteria (aldosterone > or = 200 pg/ml) was included. In summary, ARR using renin concentration is a useful screening parameter for primary aldosteronism.