Biomedical subjects

A Salvetti

Publications and source records attributed to A Salvetti.

At least 19 recordsLinked to original sources

PubMed1992

Atrial natriuretic factor in essential hypertension: echocardiographic and humoral correlates.

Aim of this study was to assess the relationship between plasma concentration of atrial natriuretic factor (ANF) and its two-dimensional echocardiographic (left ventricular mass, left atrium diameter) and humoral (plasma renin and aldosterone) variables in essential hypertension (EH). We evaluated 32 patients with uncomplicated mild to moderate EH and 10 controls. They were studied in the supine position after 7 days of constant dietary sodium intake and were off therapy since at least 3 weeks. ANF values overlapped between EH patients and controls (27.8 +/- 11.5 vs. 19.5 +/- 7.4 pg/ml, p = NS). In EH, no significant correlation was found between ANF values and left ventricular mass (r = 0.29), left atrial diameter (r = 0.04), mean arterial blood pressure (r = 0.26), plasma renin activity (r = 0.00), and aldosterone (r = 0.26). In EH, ANF values overlapped between the 15 patients with hypertrophy and the 17 patients with normal ventricular mass: 30.3 +/- 17 vs. 25.6 +/- 10.6 pg/ms (p = NS). We conclude that there is a substantial overlap in plasma ANF values between mild to moderate uncomplicated EH and controls, and left ventricular hypertrophy is not a major independent stimulus to ANF release in EH.

Adult↗

PubMed1992

Dipyridamole decreases circulating renin-angiotensin system activity in hypertensive patients.

To study the effect of adenosine on renin release, n = 6 hypertensive patients, while on a constant 80 to 100 mEq/24 h Na+ diet, received oral 150 mg dipyridamole (an adenosine uptake inhibitor) three times daily for 3 days while upright plasma renin activity (PRA) and plasma aldosterone, urinary aldosterone, plasma and urinary Na+,K+, and creatinine clearance were monitored the day before (basal) the first and third day of the treatment and the day after the withdrawal (recovery). As compared to basal and to recovery, dipyridamole significantly decreased PRA, and plasma and urinary aldosterone without affecting plasma and urinary Na+ and K+, creatinine clearance, blood pressure, and heart rate. These data, showing that dipyridamole decreases PRA and aldosterone, confirm also in hypertensives that endogenous adenosine inhibits the circulating renin-angiotensin-aldosterone system.

Adenosine↗

PubMed1992

Nonadrenergic sympathetic vascular control of the human forearm in hypertension: possible involvement of neuropeptide Y.

Animal experimental evidence suggests that neuropeptide Y (NPY) is coreleased with norepinephrine (NE) from sympathetic nerve endings and is involved in nonadrenergic neurogenic vascular control of skeletal muscle. We wished to determine whether these findings may be extended to humans. Forearm blood flow (venous occlusion plethysmography) and the regional overflows of NE and NPY-like immunoreactivity (NPY-LI) were studied at rest and during sympathetic nerve activation by lower body negative pressure (LBNP; -10 mm Hg, 10 min) in 10 hypertensive men before and after local alpha-adrenergic blockade by a dose of phenoxybenzamine (60 micrograms x 100 ml-1 x min-1 for 60 min), which most markedly attenuated responses to exogenous NE; propranolol (10 micrograms x 100 ml-1 x min-1) was present throughout. Phenoxybenzamine increased forearm blood flow at rest (11.5 +/- 1.0 vs. 3.9 +/- 0.3 ml x 100 ml-1 x min-1; p less than 0.001). LBNP-evoked reduction of forearm blood flow (37 +/- 2%, p less than 0.001) was attenuated (p less than 0.001) but not abolished (18 +/- 2%, p less than 0.001) by phenoxybenzamine. LBNP increased the overflow of NE from 5.0 +/- 1.7 to 8.2 +/- 3.0 pmol x 100 ml-1 x min-1 (p less than 0.05) and that of NPY-LI from -9.0 +/- 4.4 to 8.0 +/- 4.9 fmol x 100 ml-1 x min-1 (p less than 0.05) after phenoxybenzamine; effects on the evoked overflows of NE and NPY-LI before phenoxybenzamine were slight. Prejunctional inhibitory alpha-adrenoceptors may thus modulate NPY release as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Endothelium-dependent forearm vasodilation is reduced in normotensive subjects with familial history of hypertension.

Endothelium-dependent vasodilation is reduced in essential hypertensive subjects. To evaluate whether this abnormality is a primary defect or is a consequence of blood pressure increment, in offspring of essential hypertensive and normotensive subjects (n = 13 subjects for each group) matched for age, sex, body weight, and blood pressure, we studied the response of forearm vasculature to acetylcholine (ACh) (an endothelium-dependent vasodilator), sodium nitroprusside (a direct vasodilator of vascular smooth muscle), and forearm ischemia (13 min plus 1 min of exercise) to induce maximal vasodilation. Drugs were infused into the brachial artery at cumulative doses (ACh: 0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 ml of forearm tissue/min; sodium nitroprusside: 1, 3, and 10 micrograms/100 ml of forearm tissue/min) while forearm blood flow was measured by strain-gauge venous plethysmography. The intra-arterial blood pressure and heart rate were continuously monitored. Despite a comparable forearm vascular response to sodium nitroprusside and to forearm ischemia, the effect of ACh was significantly (p < 0.001) reduced in offspring of hypertensive subjects compared to the offspring of normotensive subjects. These data indicate that ACh-mediated forearm vasodilation is reduced in normotensive subjects with a familial history of essential hypertension, a finding that suggests that endothelium dysfunction can precede the appearance of hypertension and that this abnormality might play a role in the pathogenesis of essential hypertension.

Acetylcholine↗

PubMed1992

Adenosine activates a vascular renin-angiotensin system in hypertensive subjects.

In vitro data indicate that the activation of A2 adenosine receptors increases renin release by the accumulation of cyclic AMP. Because in human forearm vessels beta-adrenergic receptor stimulation causes the local release of renin and angiotensin II through the increase of cyclic AMP, we evaluated in six essential hypertensive subjects whether adenosine can release vascular angiotensin II. Adenosine was infused into the brachial artery at cumulatively increasing doses (0.5, 1.5, and 5 micrograms/100 ml forearm tissue per minute for 5 minutes each) during saline infusion and in the presence of the adenosine antagonist theophylline (100 micrograms/100 ml forearm tissue per minute for 15 minutes), while venous (ipsilateral deep forearm vein) and arterial (brachial artery) angiotensin II (picograms per milliliter) were measured at the end of each infusion period, and forearm angiotensin II net balance (picograms per minute) was calculated by venous-arterial differences corrected for forearm blood flow (strain-gauge venous plethysmography) and hematocrit. In control conditions, adenosine, at higher doses, caused a dose-dependent vasodilation and increased venous angiotensin II without affecting arterial values; therefore, the calculated angiotensin II net balance showed an adenosine-mediated dose-dependent release. Theophylline pretreatment blunted adenosine-mediated forearm blood flow increments and angiotensin II release. The local origin of angiotensin II was further confirmed in another group of six hypertensive subjects in whom the angiotensin converting enzyme inhibitor captopril, locally infused at the rate of 2.5 micrograms/100 ml forearm tissue per minute for 15 minutes, abolished the adenosine-mediated venous angiotensin II increments. Our data indicate that exogenous adenosine can stimulate the production of angiotensin II in the forearm vessels of hypertensive patients.

Adenosine↗

PubMed1992

Activation of sympathetic tone during dipyridamole test.

Cardiac imaging with dipyridamole infusion has been proposed as an exercise-independent tool for the diagnosis of coronary artery disease. Dipyridamole acts through the accumulation of adenosine, which reduces sympathetic tone in vasomotor nuclei of the brainstem and inhibits norepinephrine release in noradrenergic neurons but also activates arterial chemoreceptors. The aim of this study was to assess whether dipyridamole administration (up to 0.84 mg/kg over 10 minutes, a dosage commonly employed for diagnostic testing) may modulate sympathetic activity either directly or indirectly through blood pressure reduction or myocardial ischemia, which may be evoked by dipyridamole infusion and represent two recognized sympathetic stimuli. Twenty patients were studied with infusion combined with two-dimensional echocardiography and 12-lead ECG monitoring. Blood pressure was recorded each minute by a cuff sphygmomanometer. In all patients, we obtained venous blood samples for epinephrine (an index of adrenomedullary catecholamine release) and norepinephrine (an index of neuronal activity) both in resting conditions and at peak dipyridamole, ie, at the first minute after termination of dipyridamole infusion in negative cases or in the presence of obvious ischemia in positive cases (ie, as soon as a regional ventricular dyssynergy or an ST segment depression greater than 0.1 mV appeared). Epinephrine and norepinephrine determinations were made by a high performance liquid chromatography (HPLC) method. After dipyridamole, there was a significant rise in norepinephrine, while epinephrine did not change significantly. Dipyridamole-induced percentage variations of norepinephrine from baseline were not significantly correlated with mean blood pressure changes (r = .1, p = ns) and were of a similar extent in patients with (n = 10) and without (n = 10) dipyridamole-induced ischemia (+68 vs +73 percent, p = ns). Dipyridamole administration provokes an activation of sympathetic tone which can be detected even in the absence of myocardial ischemia and is not related to blood pressure changes. The increased catecholamine release appears to be of neuronal rather than adrenomedullary origin.

Adult↗

PubMed1992

Coronary microvascular disease in hypertensives.

Arterial hypertension can badly affect coronary circulation through several mechanisms that are not mutually exclusive, namely, coronary artery disease, left ventricular hypertrophy, and microvascular disease. Theoretical and experimental data suggest that coronary microvascular disease may exist in hypertensives, in whom it can cause both a reduction of coronary flow reserve and a shift to the right of the coronary flow autoregulation curve. To address this issue, we used dipyridamole- echocardiography test, which causes ischemic-like ST segment depression with no detectable changes in left ventricular function in different subsets of patients with microvascular disease (Syndrome X; Hypertrophic cardiomyopathy; acute heart rejection). We found that dipyridamole infusion can cause a similar pattern of response (i.e., echocardiographically silent ST segment depression) in mild-moderate essential hypertensives with normal epicardial coronary arteries, without left ventricular hypertrophy, with increased forearm minimal vascular resistances and with a reduced coronary reserve. This pattern of response identifies hypertensives with higher risk of ventricular arrhythmias, is amplified by acute reduction of diastolic blood pressure and can be reversed, together with the reduction of forearm vascular resistances by chronic antihypertensive treatment. Taken together these findings suggest that microvascular coronary disease can exist in hypertensives with two adverse consequences, consistent with the experimental background: the reduction of coronary flow reserve as well as a shift to the right of the coronary flow autoregulation curve.

Coronary Circulation↗

PubMed1992

Vascular tissue renin-angiotensin system in hypertensive humans.

AIM: To obtain direct evidence for and evaluate functional aspects of the vascular tissue renin-angiotensin system. METHODS: The local release of renin and angiotensin II was studied in forearm and coronary vascular beds of hypertensive hospitalized patients. The interaction between the vascular tissue renin-angiotensin system and sympathetic neurotransmission was also evaluated. RESULTS: Local beta-adrenoceptor stimulation released active and inactive renin and angiotensin II from forearm vessels, indicating the presence of a vascular tissue renin-angiotensin system in essential hypertensives. Local production of active renin and angiotensin II was closely correlated with circulating renin levels, suggesting that this vascular tissue renin-angiotensin system is at least partly dependent on uptake of renin from the circulating renin-angiotensin system. The local active renin and angiotensin II production was rapidly exhausted; this might represent a short-term control mechanism. Locally generated angiotensin II increased sympathetic vasoconstriction through the presynaptic release of noradrenaline and this effect was mediated by beta-adrenoceptor stimulation. Infusions of adenosine promoted the release of active renin and angiotensin II from the forearm and the coronary vessels.

Adenosine↗

PubMed1992

Effects of nifedipine and indomethacin on cough induced by angiotensin-converting enzyme inhibitors: a double-blind, randomized, cross-over study.

Prostaglandins (PG) have been suggested to play a role in the genesis of cough induced by angiotensin-converting enzyme inhibitors (ACE-I) and that inhibition of PG synthesis can reduce or abolish the incidence of this side effect. Moreover, experimental and clinical data suggest that nifedipine, a dihydropyridine Ca antagonist, can inhibit PG synthesis. Therefore, we wished to determine whether nifedipine can reduce cough induced by ACE-I as compared with indomethacin, a known inhibitor of PG synthesis. Fourteen hypertensive patients who developed cough during captopril chronic therapy randomly received slow-release nifedipine 20 mg twice daily (b.i.d.), indomethacin 50 mg b.i.d., and placebo b.i.d. for 1 week in a double-blind, cross-over design. At the end of each treatment phase, cough was evaluated by a self-administered questionnaire containing an ordinal scale for daily cough intensity and frequency. Indomethacin abolished or markedly reduced cough induced by ACE-I, whereas nifedipine reduced it but to a lesser degree. These findings suggest that PG can play a role in cough caused by ACE-I, and a dihydropyridine Ca antagonist can reduce the occurrence of this side effect.

Adult↗

PubMed1991

Calcium entry blockade and agonist-mediated forearm vasoconstriction in hypertensive patients. Difference between nicardipine and verapamil.

The interference by nicardipine and verapamil with the response to vasoactive stimuli, such as lower body negative pressure and angiotensin II, has been evaluated in the forearm of hypertensive patients. Forearm blood flow was monitored during the intraarterial infusion of either drug at rates equieffective on basal flow. Nicardipine blunted the peak forearm vasoconstrictor action of lower body negative pressure and a comparable result was obtained when angiotensin II was administered intraarterially. In spite of a comparable increase in forearm flow, nicardipine was more potent than verapamil in inhibiting vasoconstriction following both stimuli. Thus, nicardipine suppressed regional vascular reactivity, probably by blockade of the influx of extracellular calcium, in response to receptor activation, since both alpha-adrenergic and angiotensin II receptor-mediated vasoconstrictor responses were attenuated. However, the results of the comparison with an unrelated calcium entry blocker, such as verapamil, may suggest that nicardipine, and possibly other dihydropiridine derivatives, preferentially antagonize agonist-mediated vasoconstriction in the human forearm.

Angiotensin II↗

PubMed1991

An atrial natriuretic factor analogue at low doses attenuates forearm reflex vasoconstriction to cardiopulmonary receptor deactivation in patients with hypertension.

Contrasting data exist about a possible modulation of the autonomic function by atrial natriuretic factor (ANF) in human beings, particularly at low, biologically, significant concentrations. We have evaluated that possibility by increasing plasma ANF levels through the infusion of a synthetic analogue (WY-47,663, anaritide) in five male patients with mild to moderate uncomplicated hypertension. Nonhypotensive lower body negative pressure (-10 mm Hg x 5 min) was used to selectively deactivate cardiopulmonary receptors and to stimulate sympathetic efferent tone reflexogenically. ANF was given at either a low rate (0.005 micrograms/kg/min x 60 min, which was previously shown to increase plasma ANF in a range compatible with physiologic stimuli) or at a high rate (0.05 micrograms/kg/min x 60 min, each). Administration of ANF was preceded and followed by vehicle infusion (Haemacell x 30 min). Forearm blood flow (venous plethysmography), intraarterial blood pressure, and heart rate were monitored continuously, and venous immunoreactive ANF, plasma renin activity, aldosterone level, and venous hematocrit were measured at the end of both control and infusion periods. Arterial norepinephrine values, an indirect index of sympathetic discharge, were measured at rest and during lower body negative pressure conditions. Graded systemic ANF infusion increased immunoreactive ANF and venous hematocrit, decreased aldosterone level and plasma renin activity, whereas resting norepinephrine levels, blood pressure, and heart rate did not change. Lower body negative pressure decreased forearm blood flow during vehicle infusion, but it lost its vasoconstrictor effect during infusion of ANF. To identify the site of that inhibitory action, ANF was also infused into the brachial artery at rates that raised local but not systemic levels of immunoreactive ANF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Heterogeneous interference of nicardipine, verapamil, and diltiazem with forearm arteriolar responsiveness to adrenergic stimulation in hypertensive patients.

The interference of intraarterial nicardipine, verapamil, and diltiazem with the forearm vascular response to graded exogenous norepinephrine was evaluated in hypertensive patients. Nicardipine antagonized the vasoconstrictor effect of norepinephrine in a dose-dependent manner, whereas verapamil was ineffective, suggesting that functional alpha-adrenergic antagonism may participate in the vasodilatory and possibly the antihypertensive effect. Nicardipine also blunted the vasoconstriction to lower-body negative pressure and the action of angiotensin II administered intraarterially. Despite a comparable increase in basal forearm flow, verapamil was less potent than nicardipine in inhibiting vasoconstriction after both stimuli. Therefore nicardipine suppressed preferentially regional vascular reactivity, probably by blockade of the influx of extracellular calcium in response to receptor activation, because both alpha-adrenergic and angiotensin II receptor-mediated vasoconstrictor responses were attenuated. At variance with both nicardipine and verapamil was potentiation of the responses to norepinephrine after the administration of diltiazem. Because intraarterial propranolol abolished that potentiating action and the local vasodilatation to isoproterenol was clearly reduced, diltiazem probably interfered also with beta-adrenergic receptor-mediated vasorelaxing mechanisms in human forearm arterioles. The data further stress the heterogeneity of calcium channel blockers in humans.

Arterioles↗

PubMed1991

Calcium entry blockade and adrenergic vascular reactivity in hypertensives: differences between nicardipine and diltiazem.

The interference of nicardipine and diltiazem infused into the brachial artery at systemically ineffective rates, with the forearm vascular response to graded exogenous norepinephrine, was evaluated in hypertensive patients. Nicardipine (1 and 3 micrograms/dl forearm tissue/min in both absence and presence of propranolol) increased forearm blood flow (venous plethysmography) and antagonized dose dependently the vasoconstrictor effect of norepinephrine, suggesting that functional alpha-antagonism may participate in the vasodilating and possibly the antihypertensive effect of the drug. On the contrary, no antagonism but rather potentiation of the responses to norepinephrine occurred after diltiazem (0.5 and 1 microgram/dl forearm tissue/min). Because intra-arterial propranolol abolished that potentiating action of the drug, whereas the local vasodilation to isoproterenol was clearly reduced, diltiazem probably interfered with beta-adrenergic receptor-mediated vasorelaxing mechanisms in human forearm arterioles. The data further stress the heterogeneity of calcium entry blockers in humans.

Adrenergic alpha-Antagonists↗

PubMed1991

Theophylline is an antagonist of adenosine in human forearm arterioles.

The pharmacodynamics of theophylline in humans is attributed to the inhibition of phosphodiesterase activity, a concept based on in vitro studies using drug concentrations much higher than those achieved by therapeutic doses. Recent in vitro studies suggest that theophylline might act as an antagonist of adenosine. This hypothesis was tested in hypertensives by assessing the effect of theophylline on adenosine mediated vasodilation. Drugs were infused into the brachial artery while forearm blood flow (venous plethysmography) was continuously monitored. Adenosine, infused cumulatively (5, 15, and 50 micrograms/min for 3 min each; n = 5), caused a dose-dependent vasodilation that was clearly blunted in the presence of theophylline in a dose not affecting basal arterial flow (1000 micrograms/min for 20 min). On the contrary, papaverine, a selective phosphodiesterase activity inhibitor, infused at two increasing doses (100 and 300 micrograms/min for 20 min, n = 5), did not affect adenosine mediated vasodilation. Our data show that theophylline acts as a specific antagonist of adenosine in humans, an effect which might be relevant for its pharmacological action.

Adenosine↗

PubMed1991

Does a digoxin-like substance participate in vascular and pressure control during dietary sodium changes in patients with primary aldosteronism?

To evaluate the importance of an endogenous sodium pump inhibitor in the pathogenesis of low renin human hypertension, the urinary excretion of a digoxin-like immunoreactive substance (DLIS) was measured in eight patients with primary aldosteronism (n = 5, with adenomas) during two sequential 1-week periods of low- (20 mmol/l NaCl) and high- (200 mmol/l NaCl) sodium intake. DLIS excretion increased consistently during high-sodium intake while urinary aldosterone, plasma renin activity, cortisol and adrenocorticotropic hormone did not change. Although blood pressure showed a time-course parallel to that of the urinary DLIS, the blood pressure increments were not accompanied by evidence of vasoconstriction since forearm blood flow (plethysmographic technique) increased and forearm vascular resistances were reduced. Moreover, the reactivity of forearm arterioles to local norepinephrine was unchanged during the period of low- and high-salt intake, despite the fact that an endogenous sodium pump inhibitor should, supposedly, sensitize the responses to an adrenergic agonist. Finally, forearm vasoconstrictor responses to ouabain, a pharmacological Na+,K(+)-ATPase antagonist, were potentiated during the high-salt diet, a result not expected if an increased number of sodium pumps were occupied by an endogenous inhibitor. These results provide unequivocal evidence for a modulation by salt intake of the urinary excretion of a DLIS in patients with primary aldosteronism. This substance might participate in the regulation of body fluid volume in this syndrome and possibly in other physiological conditions. However, no evidence could be found for a cause--effect relationship between blood pressure and DLIS increments during high-salt intake, at least during the short-term course of the study.

Aldosterone↗

PubMed1991

Increased prevalence of ventricular arrhythmias in essential hypertensives with dipyridamole-induced ischemic-like S-T segment changes.

Essential hypertensives are at greater risk for ventricular arrhythmias than normotensive controls. A reduction in coronary flow reserve may be one of the mechanisms underlying this increased prevalence of ventricular dysrhythmias in hypertensives. It has previously been shown that dipyridamole infusion may provoke ischemic-like S-T segment depression in essential hypertensives with angiographically normal coronary arteries and reduced flow reserve. The aim of the present study was to assess whether electrocardiographic positivity (S-T segment depression greater than 0.1 mV from baseline) during dipyridamole testing (12-lead electrocardiogram and two-dimensional echomonitoring, with the infusion of 0.84 mg/kg dipyridamole over 10 min) might identify hypertensives at greater risk for ventricular dysrhythmias. We therefore studied 51 mild-to-moderate essential hypertensives by dipyridamole testing and 48-h Holter monitoring. All patients were off therapy for at least 2 weeks before testing and Holter evaluation. Left ventricular mass (by Penn convention) and ejection fraction (by Teichholtz rule) were evaluated by two-dimensional echocardiography. Lown classes 0-1 were found in 31 patients (Group 1) and Lown classes II-IV in 20 (Group 2). The two groups overlapped for mean blood pressure (121 +/- 9 versus 124 +/- 8 mmHg), left ventricular mass index (120 +/- 27 versus 141 +/- 42 g/m2) and left ventricular ejection fraction (54 +/- 6 versus 52 +/- 6). An electrocardiographically-positive dipyridamole test was found in seven of Group I and 16 of Group II patients (23 versus 80%, P less than 0.01). No patient showed a transient, either regional or global, systolic dysfunction during dipyridamole testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗

PubMed1991

The combination of chlorthalidone with nifedipine does not exert an additive antihypertensive effect in essential hypertensives: a crossover multicenter study.

To evaluate whether the combination of nifedipine with chlorthalidone exerts an additive antihypertensive effect when compared to single-drug treatment, 66 uncomplicated essential hypertensives, whose diastolic blood pressure was greater than 100 and less than 115 mm Hg at the end of a 1-month washout placebo period, received, according to a randomized, double-blind, crossover design, nifedipine (20 mg b.i.d.), chlorthalidone (25 mg o.d.), the two drugs combined at the same doses, and the corresponding placebo. When compared to the randomized placebo the three active treatments significantly (p less than 0.001) reduced blood pressure without changing heart rate and body weight. However, blood pressure values were similarly reduced under nifedipine and the combination and were significantly lower (p less than 0.05) than those under chlorthalidone. Moreover, the percentage of responders and normalized patients under nifedipine and the two drugs combined were similar and significantly (normalized, p less than 0.0001; responders, p less than 0.02) greater than those under chlorthalidone. Under chlorthalidone and its combination with nifedipine, plasma potassium tended to decrease and blood glucose and serum uric acid were significantly (p less than 0.05) increased. These data show that the combination of nifedipine with chlorthalidone does not exert any additive antihypertensive effect when compared to nifedipine alone and that this combination increases both blood glucose and serum uric acid. Taken together these findings indicate that the combination of a dihydropyridine calcium antagonist with a thiazide diuretic is devoid of any clinical significance in the treatment of uncomplicated essential hypertensives.

Adult↗

PubMed1991

Active and inactive renin in human forearm of hypertensive patients.

Although many in vitro and animal studies indicate the existence of a local renin--angiotensin system, data regarding its physiological role are quite controversial, and moreover, evidence suggesting inactive and active renin release from vascular tissue in vivo is lacking both in animal and humans. The aim of our study was to evaluate whether beta-adrenoceptor stimulation, a well-known stimulus to renin production, through isoproterenol might cause local renin production from vessels of the forearm of hypertensive patients. Drugs were infused into the brachial artery at systemically ineffective rates, while forearm blood flow (FBF, venous plethysmography), mean intra-arterial pressure, and heart rate were monitored throughout. Active and inactive vessel renin production was measured by calculating venous-arterial (V-A) differences by simultaneous sampling from brachial artery and an ipsilateral deep vein. Active renin (PRA) and total renin (Sepharose bound trypsin activation) were measured by radioimmunoassay while inactive renin was calculated as the difference between total and active renin. V-A differences were corrected for FBF to calculate renin extraction or production. In a group of 10 patients, isoproterenol, which was infused at increasing cumulative rates (0.03, 0.1, 0.3 micrograms.100 mL-1 forearm tissue.min-1 for 5 min each), caused a dose-dependent increment in FBF that was blunted by intra-arterial propranolol (n = 5) pretreatment (10 micrograms.100 mL-1 forearm tissue.min-1 for 10 min). beta-Adrenoceptor stimulation caused a dose-dependent outflow of both active and inactive renin, an effect antagonized by propranolol. In conclusion, our data represent the first evidence in humans of tissue active and inactive renin production in the forearm vascular bed.

Female↗