[Show abstract][Hide abstract] ABSTRACT: We sought to evaluate whether fasting hyperhomocystinemia reduces endothelial function by oxidative stress in normotensive subjects and hypertensive patients.
Subjects with hyperhomocystinemia have endothelial dysfunction.
In 23 normotensive subjects and 28 hypertensive patients, classified into normohomocystinemic and hyperhomocystinemic groups according to homocysteine plasma levels (< 8.7 and >14.6 micromol/l, respectively), we studied forearm blood flow changes (strain-gauge plethysmography) induced by intrabrachial administration of acetylcholine (0.15 to 15 microg/100 ml tissue per min) or sodium nitroprusside (1 to 4 microg/100 ml per min), an endothelium-dependent and -independent vasodilator, respectively. Acetylcholine was repeated with N(G)-monomethyl-L-arginine (L-NMMA; 100 microg/100 ml per min), vitamin C (8 mg/100 ml per min) and L-NMMA plus vitamin C.
Normotensive hyperhomocystinemic patients showed a blunted response to acetylcholine and a lower inhibiting effect of L-NMMA on acetylcholine, as compared with normohomocystinemic patients. Although vitamin C was ineffective in normohomocystinemic subjects, it increased the response to acetylcholine and restored the inhibiting effect of L-NMMA on acetylcholine in hyperhomocystinemic patients. Hypertensive hyperhomocystinemic patients showed a reduced response to acetylcholine, as compared with normohomocystinemic subjects. In both subgroups, L-NMMA failed to blunt the response to acetylcholine. The potentiating effect of vitamin C on acetylcholine was greater in hyperhomocystinemic patients than in normohomocystinemic subjects, although it restored the inhibitory effect of L-NMMA on acetylcholine-induced vasodilation to the same extent in both groups. Hyperhomocystinemia did not change the response to sodium nitroprusside.
In normotensive subjects and hypertensive patients, hyperhomocystinemia impairs endothelium-dependent vasodilation. It could be related to oxidant activity.
Journal of the American College of Cardiology 10/2001; 38(4):1106-15. · 14.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the possible relationship between hyper(H)homocysteinemia (HCY) and endothelial function in the forearm of essential hypertensive patients (EH), we studied in 28 normotensive subjects (NS, age:50.2±10.8 years; blood pressure (BP): 124.0±7.4/80.2±3.5 mmHg, HCY:12.5±7.8 μmol/L) and 55 EH (age: 49.1±8.6 years; BP: 147.4 ± 9.2/99.6±4.0 mmHg, HCY: 14.6±9.1 μmol/L) the forearm blood flow changes (FBF, strain-gauge venous plethysmography) induced by intrabrachial acetylcholine (ACH: 0.15, 0.45, 1.5, 4.5, 15 μg/100 ml/min), an END-dependent agonist, and sodium nitroprusside (SNP: 1, 2, 4 μg/100 ml/min), an END-independent agonist. We divided EH in two groups according to HCY plasma levels (HPLC method): normal HCY (15: 25.0±7.2 μmol/L, H-HCY, n=16; 48.5±10.6 years; BP: 148.3±8.4/100.2±4 mmHg): (p
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVESThe aim of the study was to evaluate whether adenosine infusion can induce production of active renin and angiotensin II in human coronary circulation.BACKGROUNDAdenosine can activate angiotensin production in the forearm vessels of essential hypertensive patients.METHODSIn six normotensive subjects and 12 essential hypertensive patients adenosine was infused into the left anterior descending coronary artery (1, 10, 100 and 1,000 μg/min × 5 min each) while active renin (radioimmunometric assay) and angiotensin II (radioimmunoassay after high performance liquid chromatography purification) were measured in venous (great cardiac vein) and coronary arterial blood samples. In five out of 12 hypertensive patients adenosine infusion and plasma samples were repeated during intracoronary angiotensin-converting enzyme inhibitor benazeprilat (25 μg/min) administration. Finally, in adjunctive hypertensive patients, the same procedure was applied during intracoronary sodium nitroprusside (n = 4) or acetylcholine (n = 4).RESULTSIn hypertensive patients, but not in control subjects, despite a similar increment in coronary blood flow, a significant (p < 0.05) transient increase of venous active renin (from 10.7 ± 1.4 [95% confidence interval 9.4 to 11.8] to a maximum of 13.8 ± 2.1 [12.2 to 15.5] with a consequent drop to 10.9 ± 1.8 [9.7 to 12.1] pg/ml), and angiotensin II (from 14.6 ± 2.0 [12.7 to 16.5] to a maximum of 20.4 ± 2.7 [18.7 to 22.2] with a consequent drop to 16.3 ± 1.8 [13.9 to 18.7] pg/ml) was observed under adenosine infusion, whereas arterial values did not change. Calculated venous–arterial active renin and angiotensin II release showed a strong correlation (r = 0.78 and r = 0.71, respectively; p < 0.001) with circulating active renin. This adenosine-induced venous angiotensin II increase was significantly blunted by benazeprilat. Finally, both sodium nitroprusside and acetylcholine did not affect arterial and venous values of active renin and angiotensin II.CONCLUSIONSThese data indicate that exogenous adenosine stimulates the release of active renin and angiotensin II in the coronary arteries of essential hypertensive patients, and suggest that this phenomenon is probably due to renin release from tissue stores of renally derived renin.
Journal of the American College of Cardiology 05/1999; · 14.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A vascular renin-angiotensin system (RAS) is present in the forearm vasculature of essential hypertensive patients and is closely related to the circulating renin profile. To test whether the haemodynamic effect of acute intrabrachial administration of captopril is related to the circulating and/or vascular RAS, 31 hypertensive patients were selected and divided into four groups according to their different circulating RAS profile (n = 7 hypertensive patients with primary aldosteronism and suppressed plasma renin activity; n = 7 low renin essential hypertensive patients; n = 8 normal renin essential hypertensive patients; n = 9 high renin renovascular hypertensive patients). The forearm net balance of active renin, plasma renin activity and angiotensin II, obtained by intrabrachial infusion of the beta-adrenergic receptor agonist isoproterenol (0.03, 0.1, 0.3 microg/100 ml/min) and calculated as the product of the venous-arterial plasma concentration gradient and forearm blood flow (FBF), was closely related to the circulating RAS. Captopril (0.25, 2.5, 25 microg/100 ml/min per 20 min each dose) unchanged basal FBF in the primary aldosteronism and low renin groups (FBF increase: from 3.9 +/- 0.4 to a maximum of 4.1 +/- 0.5 and from 3.8 +/- 0.3 to a maximum of 4.3 +/- 0.5 ml/100 ml/min, respectively), whereas it caused slight vasodilation in the normal renin group (from 3.9 +/- 0.3 to a maximum of 5.3 +/- 0.7 ml/100 ml/min), and pronounced vasodilation in the high renin group (from 4.0 +/- 0.4 to a maximum of 6.4 +/- 0.5 ml/100 ml/min). Captopril-induced vasodilation showed a significant direct correlation with the circulating and vascular RAS. The present data, while confirming the existence of a vascular RAS in the forearm of hypertensive patients indicate that the acute vasodilating effect of intrabrachial captopril is linked to a stimulated RAS, either circulating or vascular, supporting the evidence that, in acute conditions, ACE inhibitors exert their vasodilating effect through the RAS blockade.
[Show abstract][Hide abstract] ABSTRACT: Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum UCE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 microgm x ml(-1)), and by 12 hours the compound had almost disappeared (67 ng x ml(-1)). Derived t1/2 was 1.4-2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol(-1) x min(-1) x ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 24 hours) pg x ml(-1)]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg; placebo 147/100 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.
European Journal of Clinical Pharmacology 02/1995; 48(5):339-43. · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Experimental data indicate the existence of a vascular tissue renin-angiotensin system in several different vessels from various animal models. Active renin can be locally synthesized into the vessel wall or taken up from circulating plasma to produce vascular angiotensin II. Using the human forearm technique, we produced evidence indicating the release of active and inactive renin and of angiotensin II from the vessels of hypertensive patients. Moreover, the production of vascular angiotensin II seems to be strictly correlated to the circulating renin profile, suggesting the possibility that vascular renin might be at least partially taken up from plasma. To investigate a possible function of the vascular renin-angiotensin system, we studied its interaction with sympathetic neurotransmission in essential hypertensive patients. In line with animal studies, vascular angiotensin II increases the vasoconstriction induced by the stimulation of the sympathetic nervous system through the potentiation of noradrenaline release at a presynaptic level, and this effect seems to be mediated by beta-adrenoceptor activation. This facilitating effect on sympathetic neurotransmission exerted by vascular angiotensin II can be antagonized by both angiotensin II antagonists and angiotensin-converting enzyme inhibitors.
[Show abstract][Hide abstract] ABSTRACT: To evaluate whether, in the forearm of hypertensive patients with different circulating renin profiles, local beta-adrenergic receptor-induced production of active renin, plasma renin activity, angiotensin I (Ang I), and angiotensin II (Ang II) was or was not related to the renin profile, we studied four groups of patients: 1) hypertensive patients with primary aldosteronism and suppressed circulating plasma renin activity values (0.15 +/- 0.1 ng Ang I/mL per hour; n = 7), 2) essential hypertensive patients with low (0.47 +/- 0.1 ng Ang I/mL per hour; n = 8) circulating plasma renin activity values, 3) essential hypertensive patients with normal (2.48 +/- 0.52 ng Ang I/mL per hour; n = 8) circulating plasma renin activity value, and 4) renovascular hypertensive patients with high circulating plasma renin activity values (4.16 +/- 2.1 ng Ang I/mL per hour; n = 10). Isoproterenol was infused into the brachial artery, and active renin, plasma renin activity, and Ang I and Ang II forearm balance (venous-arterial differences corrected for forearm blood flow by strain-gauge plethysmography) were measured. Despite a comparable vasodilation, beta-adrenergic stimulation failed to release active renin, plasma renin activity, and Ang I and Ang II in primary aldosteronism. It slightly increased them (except for Ang I) in low renin patients but determined a local production in normal renin and renovascular hypertensive patients. The individual increments in plasma renin activity and Ang II release induced by isoproterenol showed a correlation with the renin profile.(ABSTRACT TRUNCATED AT 250 WORDS)
[Show abstract][Hide abstract] ABSTRACT: The existence of a vascular renin-angiotensin system and its role in modulating sympathetic activity were evaluated in forearm arterioles of hypertensive individuals. Isoproterenol (0.03, 0.01, 0.3 microgram/100 ml/min for 5 minutes each; n = 5) was infused into the brachial artery, and active and inactive renin, angiotensin II, and norepinephrine forearm balance (venous-arterial differences corrected for forearm blood flow by strain-gauge plethysmography) were measured. Isoproterenol caused vasodilation and a dose-dependent active and inactive renin, angiotensin II, and norepinephrine outflow, an effect blunted by propranolol (10 micrograms/100 ml/min). To evaluate the role of local angiotensin II on beta-mediated norepinephrine overflow, the experiment was repeated with captopril (2.5 micrograms/100 ml/min for 10 minutes; n = 5), which abolished angiotensin II release and significantly reduced norepinephrine overflow. To test whether angiotensin II facilitates both prejunctional norepinephrine release and its postjunctional action, we evaluated the effect of exogenous angiotensin II, infused into the brachial artery at low concentrations (0.001 microgram/100 ml/min), on forearm vasoconstriction and norepinephrine release induced by endogenous sympathetic activation (application of a lower body negative pressure: -10 and -20 mm Hg for 5 minutes, n = 10) and on the vasoconstrictor effect of local norepinephrine (0.0015, 0.005, 0.015, 0.05, 0.15 micrograms/100 ml/min for 3 minutes each; n = 6). Although angiotensin II increased the vasoconstricting effect and the norepinephrine release induced by lower body negative pressure, it failed to affect norepinephrine-mediated vasoconstriction. Our data indicate the existence in hypertensive individuals of a vascular renin-angiotensin system that seems to modulate sympathetic activity through the presynaptic facilitation of norepinephrine release.
[Show abstract][Hide abstract] ABSTRACT: Venous distensibility, forearm blood flow (FBF, plethysmographic technique), systemic blood pressure (BP), and derived forearm vascular resistances were measured in 11 borderline-mild hypertensive, otherwise healthy male subjects for a 24-h period during either placebo or transdermally delivered nitroglycerin (NTG 10 mg/24 h). The drug caused arteriolar and venular forearm vasodilation and hypotension which, although persisting throughout the 24-h observation period, reached an apparent maximum during the first hours but later tended to wane. Since NTG plasma levels were constant at that time, the data may suggest development of vascular hyporesponsiveness during continuous exposure to NTG. Venous hematocrit (Hct) decreased during transdermal NTG, indicating the plasma volume expanding action of the drug, apparently dissociated from vasodilation per se. Because no significant changes in either plasma norepinephrine (NE) or plasma renin activity occurred in these subjects, counterregulatory sympathetic or angiotensin II (AII)-mediated vasoconstriction was probably not involved in the hemodynamic action of transdermally delivered NTG.
Journal of Cardiovascular Pharmacology 11/1989; 14(4):636-41. · 2.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Simplification of radioimmunoassay procedures of urinary aldosterone-18-glucuronide was attempted, taking into consideration the aspects implied by the hydrolysis of urine and the assay itself. The procedure standardized for the hydrolysis step (samples diluted with a two-fold volume of 0.2 N HCl and incubated at 30 degrees C for 16-24 h) proved suitable in terms of practicability and accuracy. Aldosterone antisera, raised in the rabbit against an aldosterone-3-bovine albumin conjugate, were selected according to their specificity towards competing steroids. Depending on the characteristics of the antisera used, an assay of extracts, or even direct measurements of hydrolyzed urines excluding any extraction, were found to yield reliable results. In the case of a high-quality antiserum, evidence for the adequacy of assay on non-hydrolyzed urine extracts for the measurement of the excretion of unconjugated aldosterone was provided by some preliminary data. The results of the experiments, directed at the methodological and clinical validation of the simplified procedures, are reported and discussed in this paper.