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Biomedical subjects

S Taddei

Publications and source records attributed to S Taddei.

At least 109 records · Page 6Linked to original sources
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

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↗
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

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

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↗
PubMed1991

Vascular renin-angiotensin system and neurotransmission in hypertensive persons.

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.

Adult↗
PubMed1990

Atrial natriuretic factor as a vasodilator agent in hypertensive patients.

To investigate the role of Atrial Natriuretic Factor (ANF) in modulating arteriolar tone in hypertension, a synthetic 25 AA human ANF-analogue (anaritide) was infused intraarterially in the forearm vascular bed of five patients with mild hypertension. A dose-dependent increase in blood flow (plethysmographic technique) was seen at rates covering a thousand-fold range (0.008, 0.08, 0.8, 8.0 micrograms/dl tissue/min x 15 minutes each). At the lowest infusion rate, the forearm blood flow increment was associated with changes in local venous ANF concentrations comparable with those reported during biological stimuli in hypertensive man and consistent with an ANF physiologic role in forearm arterioles of hypertensive patients. However, at local venous concentrations greater than 1000 pg/ml, ANF did not relax forearm vessels by more than about one-fourth of the total forearm vasodilator capacity (as assessed through a maximally active ischemic stimulus). These data confirm the low potency of ANF as an endogenous vasodilator, although vasodilator potency is not a necessary requirement for physiologic systems involved in the regulation of muscular vascular tone. Systemic arterial pressure, heart rate, and contralateral flow did not change during the study in spite of the markedly increased peripheral ANF levels recirculating from the local forearm administration. This behavior indicates that arteriolar vasodilation is apparently not the main mechanism of action of ANF on systemic hemodynamics in hypertensive patients.

Adult↗
PubMed1990

Sympathetic nervous system-dependent vasoconstriction in humans. Evidence for mechanistic role of endogenous purine compounds.

Purine compounds modulate sympathetic neurotransmission; this modulation decreases nervous discharge by stimulating presynaptic inhibitory adenosine receptors, an effect antagonized by theophylline, and causes vasoconstriction through the stimulation of postsynaptic ATP receptors. In humans we evaluated the effect of local theophylline, which was infused into the brachial artery at the rate of 100 micrograms/100 cc/min, on the arteriolar sympathetic vasoconstriction induced by applying a lower-body negative pressure. Forearm blood flow changes were measured by strain-gauge venous plethysmography. Theophylline, which at this dosage blunted the vasodilator effect of adenosine (the physiological agonist for the P1 purinoceptor), significantly increased lower-body negative pressure-mediated vasoconstriction. To evaluate whether neurotransmitters different from norepinephrine participate in the vasoconstrictor effect of theophylline, we repeated the previous experiment in the presence of phenoxybenzamine, which was infused at a dose (60 micrograms/100 cc/min) that abolished the vasoconstrictor effect of norepinephrine. Also, after alpha-adrenoceptor blockade, theophylline continued to increase sympathetic vasoconstriction. Our data confirm that purinergic receptors and neurotransmitters also participate in endogenous sympathetic vasoconstriction in humans.

Adenosine↗
PubMed1990

Effects of insulin on hemodynamics and metabolism in human forearm.

We investigated the vascular response (blood flow and resting vascular resistance) and the metabolic response (exchange of metabolites and respiratory gases) to local insulin administration in the forearms of healthy young volunteers with the use of the perfused-forearm technique. In the postabsorptive state, the deep tissues of the forearm (mostly skeletal muscle) took up glucose (mean +/- SE 1.09 +/- 0.17 mumol.min-1.dl-1 forearm vol), beta-hydroxybutyrate (0.267 +/- 0.130 mumol.min-1.dl-1), and O2 (9.96 +/- 1.02 mumol.min-1.dl-1) and released lactate (0.284 +/- 0.098 mumol.min-1.dl-1), glycerol (0.029 +/- 0.012 mumol.min-1.dl-1), citrate (0.091 +/- 0.030 mumol.min-1.dl-1), alanine (0.184 +/- 0.044 mumol.min-1.dl-1), CO2 (7.36 +/- 0.97 mumol.min-1.dl-1), and protons (12.1 +/- 1.4 pmol.min-1.dl-1). Forearm blood flow (by venous occlusion plethysmography) was 2.95 +/- 0.18 ml.min-1.dl-1, and intra-arterial systolic/diastolic blood pressure was 116 +/- 3/76 +/- 2 mmHg. Local indirect calorimetry indicated dominance of fat as the oxidative substrate (RQ 0.76 +/- 0.09) and an energy expenditure rate of 1.03 +/- 0.11 cal.min-1.dl-1 forearm vol. One hundred minutes of intra-arterial insulin infusion (deep venous plasma insulin concn of 125 +/- 11 microU/ml) had no detectable effect on forearm blood flow, resting forearm vascular resistance, heart rate, or blood pressure. Local hyperinsulinemia significantly stimulated glucose uptake (to 4.79 +/- 0.61 mumol.min-1.dl-1 forearm vol, P less than 0.001), lactate and pyruvate release (to 0.710 +/- 0.093 and 0.032 +/- 0.016 mumol.min-1.dl-1 forearm vol, respectively; P less than 0.01 for both), potassium uptake (0.76 +/- 0.22 mueq.min-1.dl-1, P less than 0.001), and free fatty acid uptake (0.123 +/- 0.041 mumol.min-1.dl-1 forearm vol, P less than 0.05); glycerol balance switched to a net uptake (P less than 0.001), alanine release was restrained by 33% (P less than 0.05), and beta-hydroxybutyrate and citrate release were unchanged. Despite these metabolic changes, local rates of substrate oxidation and energy expenditure were not altered by insulin. In contrast, forearm proton release was significantly stimulated by insulin (to 14.8 +/- 1.4 pmol.min-1.dl-1, P less than 0.02). Proton release was also found to be directly related to resting forearm vascular resistance independent of the effect of insulin (multiple r = 0.64, P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

3-Hydroxybutyric Acid↗
PubMed1990

Calcium entry blockade and agonist-mediated vasoconstriction in hypertensive patients.

The effects of two chemically unrelated calcium channel blockers--nicardipine and verapamil--on vascular responses to exogenous norepinephrine were evaluated in uncomplicated hypertensive patients. Each drug was infused into the brachial artery at rates that did not affect systemic blood pressure or heart rate, and forearm blood flow was measured using strain gauge venous plethysmography. Nicardipine 1 microgram/100 ml forearm tissue/min dilated the forearm arterioles and antagonized the vasoconstrictor effect of norepinephrine, whereas verapamil 1 microgram/100 ml tissue/min was ineffective, even though both drugs relaxed basal tone to the same extent. The difference between nicardipine and verapamil was also evident when reflex forearm vasoconstriction was elicited by the application of a lower body negative pressure and the drugs were infused intra-arterially at 1 and 3 micrograms/100 ml tissue/min, respectively. To evaluate whether a comparable behavior might also hold for nonsympathomimetic agents, increasing doses of angiotensin II were administered to the forearm vascular bed after pretreatment with either nicardipine or verapamil. Both drugs increased forearm blood flow, but only nicardipine antagonized the effect of angiotensin II in the forearm, showing that the impairment of vasoconstrictor mechanisms was not dependent on a specific receptor. Important differences seem to exist between nicardipine and verapamil with regard to agonist-mediated vasoconstriction in hypertensive patients, which is consistent with the heterogeneity of calcium channel blockers as a pharmacological class. Preferential antagonism of a series of vasoconstrictor stimuli may characterize the vasodilatory and, possibly, the antihypertensive effect of nicardipine.

Adrenergic alpha-Agonists↗