Blood brain barrier impairment is associated with cerebrospinal fluid markers of neuronal damage in HIV-positive patients.

Blood brain barrier impairment occurs early in the course of infection by HIV and it may persist in a subset of patients despite effective antiretroviral treatment. We tested the hypothesis that HIV-positive patients with dysfunctional blood brain barrier may have altered biomarkers of neuronal damage. In adult HIV-positive highly active antiretroviral treatment (HAART)-treated patients (without central nervous system infections and undergoing lumbar punctures for clinical reasons) cerebrospinal fluid albumin to serum ratios (CSAR), total tau, phosphorylated tau, 1-42 beta amyloid, and neopterin were measured. In 101 adult patients, cerebrospinal fluid-to-serum albumin ratios were 4.8 (3.7-6.1) with 12 patients (11.9%) presenting age-defined impaired blood brain barrier. A significant correlation was observed between CSAR and total tau (p = 0.005), phosphorylated tau (p = 0.008), and 1-42 beta amyloid (p = 0.040). Patients with impaired blood brain barrier showed significantly higher total tau (201.6 vs. 87.3 pg/mL, p = 0.010), phosphorylated tau (35.3 vs. 32.1 ng/mL, p = 0.035), and 1-42 beta amyloid (1134 vs. 830 pg/mL, p = 0.045). Despite effective antiretroviral treatment, blood brain barrier impairment persists in some HIV-positive patients: it is associated with markers of neuronal damage and it was not associated with CSF neopterin concentrations.

Sympathetic and reflex abnormalities in heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy.

Congestive heart failure (CHF) is characterized by a sympathetic activation and a baroreflex impairment whose degree is directly related to the clinical severity of the disease. However, whether these abnormalities vary according to the ischaemic or idiopathic dilated nature of the CHF state has not been conclusively documented. In patients with a clinically stable, chronic CHF state in New York Heart Association functional class II and III, due either to ischaemic heart disease (IHD; n=22, age 60.3+/-2.4 years, means+/-S.E.M.) or to idiopathic dilated cardiomyopathy (IDC; n=20, age 58.9+/-2.8 years), and in 30 age-matched controls, we measured arterial blood pressure (using a Finapres device), heart rate (by electrocardiogram) and postganglionic muscle sympathetic nerve traffic (by microneurography) at rest and during baroreceptor manipulation induced by the vasoactive drug-infusion technique. Blood pressure values were not significantly different in CHF patients and controls. Compared with controls, heart rate was similarly increased and left ventricular ejection fraction (by echocardiography) similarly reduced in CHF patients with IHD or IDC. Muscle sympathetic nerve traffic was significantly greater in CHF patients than in controls, and did not differ between patients with IHD or IDC (67.3+/-4.2 and 67.8+/-3.8 bursts/100 heart beats respectively). This was also the case for the degree of baroreflex impairment. These data show that CHF states due to IHD or to IDC are characterized by a similar degree of peripheral sympathetic activation and by a similar impairment of the baroreflex function. Thus the neuroadrenergic and reflex abnormalities characterizing CHF are independent of its aetiology.

Sympathetic and reflex alterations in systo-diastolic and systolic hypertension of the elderly.

BACKGROUND: Previous studies have shown that young and middle-aged essential hypertensives are characterized by a sympathetic activation coupled with an impaired baroreflex-heart rate control. The present study aimed to determine whether these neuroadrenergic and reflex alterations also characterize systo-diastolic and systolic hypertension of the elderly. SUBJECTS AND METHODS: In 20 untreated elderly essential hypertensive subjects [10 with a systo-diastolic and 10 with an isolated systolic hypertension, aged 67.2 +/- 1.5 years and 66.9 +/- 1.7 years (mean +/- SEM)], we measured beat-to-beat arterial blood pressure (finger photoplethysmographic device), heart rate (electrocardiogram) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Data were compared with those obtained in 11 age-matched normotensive control subjects. RESULTS: Compared to the elderly normotensive group, muscle sympathetic nerve activity was increased to a similar degree in the group of systo-diastolic and systolic hypertension (50.8 +/- 4.2 versus 75.2 +/- 5.2 and 70.4 +/- 5.1 bursts per 100 heart beats, respectively, P< 0.01 for both). In the control group, the stepwise increase in arterial pressure induced by phenylephrine caused progressive bradycardia and sympathoinhibition, while the stepwise decrease in arterial pressure had opposite effects. While baroreceptor-heart rate control was markedly impaired (average reduction 41.6%), in both systo-diastolic and systolic hypertensive patients, baroreceptor modulation of sympathetic nerve traffic was similar to that seen in normotensive individuals. CONCLUSIONS: These data demonstrate that sympathetic activation is not only a feature of young and middle-aged, but also of elderly hypertensives, regardless of whether both systolic and diastolic or only systolic blood pressure is increased. They also show that hypertension of the elderly is not accompanied by an impaired baroreceptor modulation of sympathetic nerve traffic.

Sympathoexcitatory responses to the acute blood pressure fall induced by central or peripheral antihypertensive drugs.

This study was designed to evaluate the effects of an acute blood pressure reduction brought about by a peripheral vasodilator agent (prazosin) or by a drug combining central and peripheral modes of action (urapidil), on three markers of adrenergic tone such as muscle sympathetic nerve traffic (MSNA), venous plasma norepinephrine (NE), and heart rate (HR). In 12 untreated essential hypertensives (age, 50.7 +/- 1.9 years; mean +/- SEM), we evaluated in two experimental sessions, according to a double-blind crossover design, the effects of acute oral administration of 2 mg prazosin or 30 mg urapidil on beat-to-beat finger blood pressure (Finapres), HR (electrocardiogram), NE (high-performance liquid chromatography), and MSNA (microneurography at a peroneal nerve). In each session measurements were performed in the no-drug control state and repeated throughout a 3-h period after drug administration. For similar blood pressure reductions, the two drugs caused similar increases in NE and MSNA (peak effects: NE = +1.1 +/- 0.2 vs 0.9 +/- 0.2 nmol/L and MSNA = +10.9 +/- 1.8 vs +10.1 +/- 1.6 bursts/min for prazosin and urapidil respectively, P = ns between drugs), whereas HR increased more markedly after prazosin administration (+6.1 +/- 1.1 vs +2.4 +/- 0.8 beats/min, P < 0.05). These data provide evidence that acute blood pressure reductions induced by antihypertensive drugs with central or peripheral modes of action activate the sympathetic nervous system to a similar extent. Thus adrenergic activation is not peculiar to vasodilators but rather generalized to any drug-induced acute blood pressure fall, presumably because of the lack of a baroreflex resetting, which occurs during chronic but not during acute antihypertensive treatment.

New drugs for the treatment of hypertension.

Despite the many outstanding favorable results achieved in the treatment of hypertension, several unmet goals of antihypertensive therapy remain, such as better blood pressure control, greater protection against the organ damage associated with hypertension, better tolerability, and ultimately a more effective prevention of cardiovascular disease. These unmet goals are the reasons why new antihypertensive drugs are synthesized and tested in the clinical practice. This paper briefly mentions the goals of new antihypertensive agents and examines the main pharmacological and clinical features of new classes of antihypertensive drugs, such as angiotensin II receptor blockers, central agents, vasopeptidase inhibitors, and endothelin antagonists. The results of experimental and clinical studies with these new drugs are reviewed, emphasizing some advantages and potential disadvantages of these drugs compared with traditional antihypertensive drugs.

Fluctuations of radial artery distensibility throughout the menstrual cycle.

Estrogen administration has a number of favorable cardiovascular effects, and recent evidence suggests that these include an increase in arterial distensibility. Whether this is also the case for the physiological changes in estrogen production during the menstrual cycle has never been determined, however. In 21 premenopausal healthy women, we continuously measured radial artery diameter and blood pressure by an echo-tracking device and a beat-to-beat finger device, respectively. Arterial distensibility was calculated as distensibility/blood pressure curve. The measurements were made during the follicular, ovulatory, and luteal phases of the menstrual cycle. As expected, compared with the follicular phase, plasma estradiol, follicle-stimulating hormone, luteinizing hormone, and prolactin were increased in the ovulatory phase, whereas progesterone was increased in the luteal phase, together with antidiuretic hormone. Radial artery distensibility was increased in the ovulatory and reduced in the luteal phase, the changes being independent of the small, concomitant blood pressure changes. The arterial wall stiffening seen in the luteal phase was associated with a reduction in the flow-dependent endothelial dilatation of the radial artery as assessed by the hyperemia after short-term ischemia of the hand. Thus, the natural menstrual cycle is characterized by alterations in radial artery distensibility. The mechanisms responsible for this phenomenon remain to be clarified. It is possible, however, that the greater arterial distensibility of the ovulatory phase is due to an estrogen-dependent reduction in vascular smooth muscle tone, whereas the arterial stiffening of the luteal phase depends on vascular smooth muscle contraction due to more complex hormonal phenomena, ie, an endothelial impairment due to estrogen reduction but also to an increase in progesterone and antidiuretic hormone levels.

Seasonal variations in home and ambulatory blood pressure in the PAMELA population. Pressione Arteriose Monitorate E Loro Associazioni.

OBJECTIVE: Clinic blood pressure values are known to change according to seasonal influences. We therefore examined home and 24 h ambulatory blood pressure values to determine whether these measurements are also affected by the seasons. DESIGN AND METHODS: In 2051 subjects of the Pressione Arteriose Monitorate E Loro Associazioni (PAMELA) study, we measured clinic (sphygmomanometric measurements), home (semi-automatic device) and ambulatory (Spacelabs 90207) systolic blood pressure, diastolic blood pressure and heart rate. Because the overall sample was evenly distributed over each month (except August), we were able to make a cross-sectional determination of whether the values differed between seasons. The corresponding heart rates were also evaluated. RESULTS: As expected, summer was associated with the lowest clinic blood pressure and winter with the highest, and this was the case also for home and 24 h average blood pressure, although seasonal differences in the latter were less pronounced. Seasonal clinic, home and ambulatory blood pressure patterns were similar for normotensive subjects (n = 1152), untreated hypertensives (n = 540) and treated hypertensives (n = 359). Heart rate values did not differ by season. CONCLUSIONS: Seasonal influences on blood pressure are not limited to conventional measurements but characterize daily values as well. These effects are visible in both normal and elevated blood pressure values, regardless of the effect of antihypertensive drugs. This has implications both for the clinician and for studies aimed at evaluating the effects of antihypertensive treatment.

Heart rate as marker of sympathetic activity.

OBJECTIVE: To determine the value of the supine heart rate as a marker of sympathetic tone by assessing, in a large group of subjects, the relationships between this parameter and two other indices of sympathetic activity, plasma norepinephrine and sympathetic nerve traffic. PATIENTS AND METHODS: We studied 243 subjects aged 50.0+/-12.1 years (mean +/- SD). Of these, 38 were normotensive healthy controls, 113 subjects had untreated essential hypertension, 27 were obese normotensives and 65 had congestive heart failure. In each subject, over a 10 min supine period, we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), venous plasma norepinephrine (high-performance liquid chromatography) and efferent postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). RESULTS: In the whole study group, supine heart rate was correlated with both plasma norepinephrine (r = 0.32, P < 0.0001) and muscle sympathetic nerve activity (r = 0.38, P < 0.0001). This was also the case in the normotensive obese subjects and the heart failure subjects considered separately. Heart rate values were greater in the obese and the heart failure patients than in controls (75.1+/-13.0 and 78.2+/-13.0 versus 69.2+/-11.6 beats/min; P < 0.05 and P < 0.001, respectively), as were plasma norepinephrine (362.7+/-202 and 400.3+/-217 versus 230.4+/-126 pg/ml; P < 0.01 and P < 0.001, respectively) and muscle sympathetic nerve activity (44.1+/-14.7 and 55.3+/-14.3 versus 27.8+/-11.0 bursts/min; P < 0.001 for both). In contrast, in the essential hypertensive subjects, no significant relationship was found between these three indices of sympathetic activity. Furthermore, in the hypertensives, the heart rate was not increased, at variance with the sympathetic nerve traffic, which was greater than in controls (36.2+/-10.0 versus 27.8+/-11.0 bursts/min, P < 0.001). CONCLUSIONS: These data suggest that the supine heart rate can be regarded as a marker of intersubject differences in sympathetic tone, and that this is the case both in the general population and in those with cardiovascular diseases. Its value for this purpose is limited, however, and the limitations may be more evident in essential hypertension than in conditions such as obesity and heart failure.

Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension.

BACKGROUND: Human studies have shown that the blood pressure lowering effects of angiotensin converting enzyme inhibitors are accompanied by a reduction in plasma norepinephrine levels. Whether this is due to central or peripheral mechanisms is unknown, however. OBJECTIVE: To evaluate the effects of chronic interference with the renin-angiotensin system on sympathetic nerve traffic and baroreflex control of vagal and adrenergic cardiovascular drive. PATIENTS AND METHODS: In 18 untreated mild to moderate essential hypertensive patients aged 48.5+/-1.9 years (mean+/-SEM), we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), plasma renin activity (radioimmunoassay), plasma norepinephrine (high-performance liquid chromatography) and postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). In nine patients, measurements were performed before and after 2 months of oral administration of lisinopril (10 mg/day), while in the remaining nine patients they were performed before and after a 2 month observation period, without the drug administration. Measurements were performed at rest and during baroreflex stimulation and deactivation elicited by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. RESULTS: Lisinopril induced a marked increase in plasma renin activity (from 1.1+/-0.2 to 6.4+/-1.3 ng/ml per h, P< 0.01) and a reduction in mean arterial pressure (from 109.6+/-3.1 to 98.7+/-2.9 mmHg, P < 0.01) without affecting the heart rate. Plasma norepinephrine and muscle sympathetic nerve activity values were not significantly different before and after lisinopril treatment (plasma norepinephrine values changed from 290.4+/-39.2 to 308.1+/-67.1 pg/ml; muscle sympathetic nerve activity changed from 56.4+/-5.3 to 50.6+/-6.6 bursts/100 heart beats). Neither the sympathoinhibitory nor the sympathoexcitatory responses to phenylephrine and nitroprusside were affected by lisinopril, nor the concomitant bradycardia and tachycardia. The curves relating mean arterial pressure to heart rate and muscle sympathetic nerve activity values during baroreceptor manipulation were shifted to the left, indicating a resetting of the baroreflex to the lower blood pressure values achieved during treatment. CONCLUSIONS In essential hypertension, sympathetic nerve traffic is not affected by chronic angiotensin converting enzyme inhibitor treatment that effectively interferes with the renin-angiotensin system and lowers the elevated blood pressure. The baroreflex ability to modulate heart rate and central sympathetic outflow is also unaffected. These data argue against the existence of a central sympathoexcitatory effect of angiotensin II in this condition. They also indicate that antihypertensive treatment with an angiotensin converting enzyme inhibitor preserves autonomic reflex control, with favorable consequences for cardiovascular homeostasis.

Effects of isolated systolic hypertension and essential hypertension on large and middle-sized artery compliance.

BACKGROUND: Systolic hypertension of the elderly is characterized by a reduction in arterial compliance. Whether and to what extent this involves arteries of various structure and size is not well known. OBJECTIVE: To study carotid and radial artery compliance in systolic hypertension of the elderly, compared to essential hypertension and normotension. METHODS: We investigated 28 elderly patients with systolic hypertension (age 68.6 +/- 1.4 years, mean +/- SE; systolic blood pressure > 160 mmHg and diastolic blood pressure < 90 mmHg) plus 17 age-matched patients with essential hypertension and 15 age-matched healthy normotensive subjects. Radial and carotid artery compliance were evaluated using echotracking techniques. In both arteries compliance was assessed statistically and dynamically, i.e. as compliance values throughout the diasto-systolic pressure range. Measurements included intima-media wall thickness of the radial artery. RESULTS: Compared to normotensive subjects, carotid artery compliance was reduced in essential hypertension and more so in systolic hypertension. However, although in both groups radial artery wall thickness was markedly greater than in the normotensive group, radial artery compliance was markedly reduced in systolic hypertension, but unchanged in essential hypertension. CONCLUSIONS: In systolic hypertension of the elderly the reduction of arterial compliance is marked in both muscular and large elastic arteries, while in elderly essential hypertensives changes in arterial compliance are more heterogeneous, i.e. only carotid artery compliance is reduced. The different effects of these two types of hypertension on arterial mechanics are visible throughout the physiological range of blood pressure and probably accounted for by different alterations in vessel wall structure.

Combined effects of hypertension and hypercholesterolemia on radial artery function.

Compliance and distensibility of middle-sized conduit arteries are increased in hypertension and reduced in hypercholesterolemia. Despite their frequent association in the same individual, the combined effect of these two conditions on arterial mechanical properties is unknown. We studied four groups of age- and sex-matched subjects: 10 normotensive normocholesterolemic subjects, 10 mild hypertensive normocholesterolemic subjects, 10 mild hypercholesterolemic normotensive subjects, and 10 mild hypertensive and mild hypercholesterolemic subjects. We measured radial artery diameter by an echotracking device and beat-to-beat blood pressure from an ipsilateral finger. Compliance-pressure and distensibility-pressure curves were derived by Langewouters' formula. Between-group comparisons were made by calculating for both compliance and distensibility the integral of the area under the portion of the curve common to the four groups ("isobaric" compliance and distensibility). Blood pressure was similarly elevated in the two hypertensive groups, and serum cholesterol was similarly elevated in the two hypercholesterolemic groups. Compared with values in normotensive normocholesterolemic subjects, isobaric compliance and distensibility were greater in hypertensive normocholesteroclemic (+38% and 47%, respectively) and smaller in normotensive hypercholesterolemic (-6% and -23%) subjects. However, when both hypertension and hypercholesterolemia were present, isobaric compliance and isobaric distensibility were significantly reduced (-26% and -18%, P < .05). Therefore, hypercholesterolemia reverses the effect of hypertension on arterial compliance and causes arterial stiffening, as when present alone.

Differential alterations of common carotid and femoral artery distensibility in 12-week-old spontaneously hypertensive rats.

OBJECTIVE: In essential hypertension, the mechanical properties of the radial artery have been shown to be largely unaltered, whereas more controversial and less reliable data have been obtained for the common carotid artery. We therefore examined the distensibility/pressure relationships of the predominantly elastic common carotid artery and of the predominantly muscle-type femoral artery in 12-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). METHODS: Eleven 12-week-old SHR and 10 age-matched WKY rats were anesthetized with sodium pentobarbitone. Blood pressure and pulse rate were measured by catheters inserted in the common carotid and in the femoral arteries, while contralateral arterial diameter was continuously recorded via an echo-tracking device. Arterial compliance was derived according to the Langewouters formula, and its values were normalized for the diameter, to obtain distensibility/pressure curves and to calculate the distensibility index. The Peterson elastic modulus was also calculated in order to obtain a pressure-independent estimate of arterial mechanical properties. RESULTS: Femoral artery distensibility/pressure curves and distensibility index were similar in the two groups of rats, the latter being 1.13+/-0.13 mm/mmHg10(-3) in SHR and 1.28+/-0.15 mm/mmHg10(-3) in WKY rats (means+/-SEM; NS). In contrast, in SHR, common carotid artery mechanical properties were clearly impaired, as shown by a marked reduction in distensibility index (2.55+/-0.16 mm/mmHg10(-3) in SHR versus 3.4+/-0.3 mm/mmHg10(-3) in WKY rats; P< 0.05), and by a significant increase in the Peterson elastic modulus. CONCLUSIONS: In the SHR model, high blood pressure alters the mechanics of large arteries even in the relatively early stage of the disease; however, the alterations are not homogeneous inasmuch elastic-type vessels are affected to a much greater extent than muscle-type vessels.

Large and medium sized artery abnormalities in untreated and treated hypothyroidism.

BACKGROUND: Hypothyroidism is frequently accompanied by cardiac dysfunction, increased vascular resistance and a greater prevalence of hypertension. Whether this condition is also accompanied by alterations of large artery function and structure is not known, however. PATIENTS AND METHODS: We investigated radial artery compliance and wall thickness as well as carotid artery compliance in 11 normotensive recently diagnosed and never treated hypothyroid patients. Fifteen euthyroid healthy age- and sex-matched subjects served as controls. No subject had evidence of large artery atherosclerotic lesions. Carotid artery diameter was evaluated continuously by a B-M mode device and carotid compliance obtained by the Reneman formula. Radial artery diameter and wall thickness were continuously acquired over the systodiastolic blood pressure range (beat-to-beat finger measurement) by an echo-tracking device, and compliance (Langewouters formula) was expressed as the integral of the area under the compliance/blood pressure curve normalized for pulse pressure. RESULTS: Patients with hypothyroidism showed greater radial wall thickness (+109%, P < 0.01) and compliance (+58%, P < 0.03) than controls. Carotid artery compliance was not different in the two groups. In 10 hypothyroid patients L- tiroxine therapy for 9.0 +/- 2.3 months did not change carotid artery function but markedly reduced radial artery wall thickness (-36%, P < 0.05) and compliance (-20%, P < 0.05). CONCLUSIONS: Hypothyroidism is associated with early arterial structural and functional alterations, which involve more muscular than elastic arteries. These alterations, however, are reversible by hormonal replacement therapy.

Impaired radial artery compliance in normotensive subjects with familial hypercholesterolemia.

Hypercholesterolemia impairs arteriolar dilatation, but whether the vascular abnormalities accompanying this condition include large artery function is unknown. We addressed this issue in 13 normotensive subjects with familial hypercholesterolemia (serum cholesterol 401.6 +/- 16.9 mg/dl, mean +/- S.E., FHC) and no evidence of atherosclerotic lesions, in whom radial artery (RA) diameter and blood pressure (BP) were measured beat to beat by an echotracking and a Finapres device, respectively. RA compliance (RAC) was derived from the diameter/BP relationship and expressed over the systo-diastolic BP range, both at baseline and after a 12-min brachial artery occlusion. RAC was expressed also as the area under the RAC/BP curve divided for pulse BP. Measurements included maximal forearm blood flow (plethysmography) and minimal forearm vascular resistance (FVR) which were obtained from the values following the 12-min brachial arterial occlusion. Data were collected before and after 6- and 24-month lipid lowering treatment (simvastatin 40 mg/day). Ten age-matched normotensive normocholesterolemic healthy subjects (N) served as controls. Compared to N, baseline RAC was strikingly reduced in FHC (-53.5%, P < 0.01). After ischemia RAC increased significantly and markedly in N (+38.7, P < 0.01), while only a modest and non-significant increase was observed in FHC. Minimal FVR was markedly higher in FHC than in N (3.5 +/- 0.9 vs 1.6 +/- 0.1 units, P < 0.01). In FHC (7 subjects) RAC remained unchanged after 6 months of lipid lowering treatment, but increased markedly (+55.2%, p < 0.05) when treatment was prolonged to 24 months. Lipid lowering treatment also reduced minimal FVR, the effect being significant both after 6 and after 24 months. No changes in RAC and minimal FVR were seen after 6 months in controls. Thus, in subjects with a marked increase in serum cholesterol due to FHC, not only arteriolar dilatation, but also RAC and distensibility are markedly impaired. This impairment can be favourably affected by an effective lipid lowering treatment of long duration.

Angiotensin-converting enzyme inhibition and radial artery compliance in patients with congestive heart failure.

Congestive heart failure is characterized by a clear-cut impairment of arterial compliance of medium-sized arteries, but whether this alteration is irreversible or can be favorably affected by cardiovascular drugs currently used in congestive heart failure treatment is unknown. We studied 9 congestive heart failure patients (New York Heart Association class II; age, [mean +/- SEM] 60.7 +/- 3.3 years) receiving diuretic and digitalis treatment in whom arterial compliance was assessed at the level of the radial artery by an echotracking device capable of measuring the arterial diameter along the entire cardiac cycle. Beat-to-beat arterial blood pressure was concomitantly measured by a Finapres device that allowed diameter-pressure curves and compliance-pressure curves (Langewouters' formula) to be calculated for the entire systolic-diastolic blood pressure range. Arterial compliance was expressed as the area under the compliance-pressure curve normalized for pulse pressure (compliance index). Data were collected before and after 4 and 8 weeks of oral administration of benazepril (10 mg/day). Ten healthy subjects were studied before and after an observational period of 4 weeks (5 subjects) or 8 weeks (5 subjects), and 9 age-matched mildly essential hypertensive subjects studied before and after 4 to 12 weeks of benazepril administration served as control subjects. In congestive heart failure patients, baseline compliance index was significantly less than in normotensive and hypertensive subjects. However, the compliance index showed a marked increase after 4 weeks of benazepril administration (+95.7 +/- 24.9%, P < .05); the increase was also marked after 8 weeks of angiotensin-converting enzyme inhibitor treatment (+77.7 +/- 4.2%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations of radial artery compliance in patients with congestive heart failure.

Congestive heart failure is accompanied by several hemodynamic alterations. To investigate whether these alterations include reduced arterial compliance, we studied 25 patients (age 57 +/- 2 years, mean +/- SE) with a mild or severe congestive heart failure based on clinical symptoms (New York Heart Association class II vs III or IV) and on echocardiographic alterations of left ventricular diastolic diameter and ejection fraction. Radial artery diameter and blood pressure were continuously measured by Doppler ultrasonography and a finger pressure device, respectively. Compliance was calculated by the Langewouters formula, and compliance values were derived throughout the systolic-diastolic pressure range. The area under the compliance-pressure curve normalized for pulse pressure was used to compare compliance values in the various groups. Data were obtained both in baseline condition and at the release from a 12-minute brachial artery occlusion. Fourteen healthy, age-matched subjects served as controls. Compared with the control group, patients with severe congestive heart failure showed a reduction of baseline compliance index (-48%, p < 0.01). Furthermore, while in control subjects compliance markedly increased after brachial artery occlusion (+43%, p < 0.01), in patients with severe congestive heart failure no increase occurred. No baseline compliance alteration was seen in patients with mild congestive heart failure in whom, however, the postischemic increase in compliance was also significantly blunted (-50% vs controls, p < 0.05). Thus, arterial compliance and arterial compliance modulation are impaired in congestive heart failure. Although more marked in severe congestive heart failure, the impairment is manifest in mild congestive heart failure as well.