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S Taddei

Publications and source records attributed to S Taddei.

At least 73 records · Page 4Linked to original sources
PubMed1997

Role of cysteine residues of rat A2a adenosine receptors in agonist binding.

In the present study, we investigated the role of disulfide bridges and sulfhydryl groups in A2a adenosine receptor binding of the agonist 2-p-(2-carboxyethyl)phenylethylamino)-5'-N-ethylcarboxamidoadenosi ne (CGS 21680). To evaluate the presence of essential disulfide bridges, rat striatal membranes were incubated with [3H]CGS 21680 in the presence of dithiothreitol and binding of the agonist to membranes was measured. The amount of [3H]CGS 21680 which specifically bound, decreased progressively upon pretreatment of membranes with increasing concentrations of dithiothreitol. Pretreatment of rat striatal membranes with 12.5 mM dithiothreitol for 15 min at 25 degrees C resulted in a 2-fold decrease of A2a adenosine receptor affinity for [3H]CGS 21680, and a reduction in the maximal number of binding sites. The presence of agonist or antagonist ligands protected the A2a adenosine receptor sites from the effect of dithiothreitol. We also examined the susceptibility of A2a adenosine receptors to inactivation by the sulfhydryl alkylating reagent, N-ethylmaleimide. When rat striatal membranes were pretreated with N-ethylmaleimide for 30 minutes at 37 degrees C, a decrease in specific [3H]CGS 21680 binding was observed. Pretreatment of membranes with 1 mM N-ethylmaleimide also resulted in a 2-fold reduction of A2a adenosine receptor affinity for [3H]CGS 21680, as well as a slight decrease in the maximal number of binding sites. Neither agonist nor antagonist ligands were effective in protecting the receptor sites from inactivation by N-ethylmaleimide. In contrast, addition of 100 microM guanosine-5'-O-(3-thiotriphosphate) or 5'-guanylylimidodiphosphate were both effective in protecting the receptor sites from inactivation by N-ethylmaleimide. This protective effect was significant but not complete. Our data suggest that disulfide bridges play a role in the structural integrity of the A2a adenosine receptor, furthermore, reduced sulfhydryl groups appear to be important but we do not yet know if they are on the receptor or on the Gs alpha subunit.

Adenosine↗
PubMed1997

Microalbuminuria and renal haemodynamics in essential hypertension.

The present study was designed to evaluate the renal haemodynamic pattern of never-treated microalbuminuric and normoalbuminuric patients with essential hypertension. A total of 19 never-treated essential hypertensive patients with microalbuminuria were selected and, as control subjects, 24 never-treated essential hypertensive patients without microalbuminuria (determined on three 24-h urine collections) were recruited. In the two groups, we compared blood pressure values, standing plasma noradrenaline, plasma renin activity, plasma aldosterone, urinary aldosterone, lipid profile, serum glucose and uric acid, glomerular filtration rate and renal plasma flow. In comparison with normoalbuminuric patients, microalbuminuric patients showed significantly higher systolic blood pressure values (P < 0.05), higher renal vascular resistances (P < 0.05) and lower plasma renin activity values (P < 0.01). Urinary albumin excretion showed a significant positive correlation with systolic (r = 0.46, P < 0.005) and mean blood pressure (r = 0.38, P < 0.05), serum uric acid (r = 0.43, P < 0.005) and triglyceride values (r = 0.36, P < 0.005), and a significant negative correlation with plasma renin activity (r = -0.34, P < 0.05). The present data are consistent with the occurrence of renal vasoconstriction in microalbuminuric never-treated essential hypertensive patients.

Adult↗
PubMed1997

Cutaneous vasodilation to acetylcholine in patients with essential hypertension.

Endothelium-dependent vasodilation is reduced in the forearm of patients with essential hypertension. To evaluate whether endothelium-dependent vasodilation is also reduced in the skin microcirculation of patients with essential hypertension, we evaluated the effect of acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside, an endothelium-independent vasodilator, on cutaneous and total forearm blood flow in normotensive subjects (n = 8) and matched patients with essential hypertension (n = 9). We infused acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 ml forearm tissue/min) and sodium nitroprusside (1, 2, and 4 microg/100 ml forearm tissue/min) into the brachial artery, and we measured cutaneous blood flow (laser Doppler flowmeter) and muscle blood flow (strain-gauge venous plethysmography) modifications. Both the cutaneous and muscle blood flow increases induced by acetylcholine were reduced in patients with essential hypertension as compared with normotensive controls, whereas the skin and muscle vasodilation induced by sodium nitroprusside was similar in the two groups of patients. These data confirm the impairment of endothelium-dependent vasodilation in the muscle vascular bed of patients with essential hypertension and demonstrate the presence of endothelial dysfunction in skin microcirculation.

Acetylcholine↗
PubMed1997

Endogenous estrogen and acetylcholine-induced vasodilation in normotensive women.

Acute exogenous estrogen administration enhances endothelial function in postmenopausal women. To evaluate the effect of endogenous estrogen on endothelium-dependent vasodilation, in 10 fertile normotensive women (age range 45 to 51 years) we studied the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 1.5 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator, in basal conditions and within 1 month after ovariectomy. As control subjects, 10 matched healthy women were also evaluated. In basal condition, vasodilation to acetylcholine and sodium nitroprusside was similar in patients and control subjects. Ovariectomy was followed by endogenous estrogen deprivation (from 71.6 +/- 31.3 to < 12 pg/mL) and was associated with a significant (P < .01) reduction in acetylcholine-induced vasodilation compared with baseline (maximum percent increase in forearm blood flow: baseline 568.2 +/- 47.1%; ovariectomy 309.5 +/- 37.4%); the response to sodium nitroprusside was unaffected by ovariectomy (maximum percent increase in forearm blood flow: baseline 526.4 +/- 36.5%; ovariectomy 454.7 +/- 47.2%; P = NS). In 6 of 10 patients, the study was repeated after 3 months of estrogen replacement therapy (17 beta-estradiol, 50 micrograms/d by transdermal patches). Exogenous estrogen restored acetylcholine-induced vasodilation (maximum percent increase in forearm blood flow: 548.9 +/- 43.1%; P < .01 versus ovariectomy), which was no longer different from baseline, whereas the response to sodium nitroprusside was not affected (maximum percent increase in forearm blood flow: 480.2 +/- 39.3%; P = NS). These results suggest a protective role of endogenous estrogen on endothelium-dependent vasodilation in the forearm vascular bed of normotensive women.

Acetylcholine↗
PubMed1997

Cyclooxygenase inhibition restores nitric oxide activity in essential hypertension.

To evaluate whether cyclooxygenase constrictor substances can impair nitric oxide-mediated vasodilation in essential hypertension, in seven normotensive subjects (43.3 +/- 4.1 years; BP, 117 +/- 6/81 +/- 2 mm Hg) and seven essential hypertensive patients (47.1 +/- 5.2 years; BP, 151 +/- 8/98 +/- 4 mm Hg) we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 15 micrograms.100 mL-1.min-1) in basal conditions, during infusion of NG-monomethyl-L-arginine (L-NMMA; 100 micrograms.100 mL-1.min-1), a nitirc oxide synthase inhibitor, or indomethacin (50 micrograms.100 mL-1.min-1), a cyclooxygenase inhibitor, or simultaneous indomethacin and L-NMMA. In normotensives, vasodilation to acetylcholine was blunted by L-NMMA (maximum flow increase: 671 +/- 64% and 386 +/- 42%, respectively; P < .01), and this effect was unchanged by indomethacin. In contrast, in hypertensive patients, vasodilation to acetylcholine (maximum flow increase: 458 +/- 33%) was unchanged by L-NMMA. Indomethacin significantly (P < .01) increased the response to acetylcholine (maximum flow increase: 635 +/- 53%) and restored the inhibitory effect of L-NMMA (maximum flow increase: 445 +/- 36%; P < .01 versus indomethacin alone). In an adjunctive seven normotensives (51.4 +/- 4.2 years; BP, 114 +/- 5/79 +/- 3 mm Hg) and seven essential hypertensives (53.2 +/- 7.6 years; BP, 153 +/- 9/100 +/- 3 mm Hg) we repeated the same protocol by replacing L-NMMA with L-arginine (200 micrograms.100 mL-1.min-1), the substrate for NO synthase. In normotensives, vasodilation to acetylcholine was increased by L-arginine (maximum flow increase: 539 +/- 48% and 806 +/- 61%, respectively) and this effect was unchanged by indomethacin. In hypertensive patients, vasodilation to acetylcholine (maximum flow increase: 339 +/- 32%) was unchanged by L-arginine but was significantly (P < .01) increased by indomethacin (maximum flow increase: 592 +/- 38%). Moreover, indomethacin restored the facilitatory effect of L-arginine (maximum flow increase: 804 +/- 56%; P < .01 versus indomethacin alone). Therefore, cyclooxygenase inhibition restores nitric oxide-mediated vasodilation in essential hypertension, suggesting that cyclooxygenase-dependent substances can impair nitric oxide production.

Acetylcholine↗
PubMed1997

Hypertension causes premature aging of endothelial function in humans.

We designed the present study to evaluate whether in normotensive subjects and hypertensive patients aging causes endothelial dysfunction by a defect in the L-arginine-nitric oxide pathway or production of cyclooxygenase-dependent vasoconstrictors. In 43 normotensive subjects and 47 essential hypertensive patients, we evaluated forearm blood flow (strain-gauge plethysmography) modifications evoked by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator, in the presence of saline, L-arginine (1 micromol/100 mL per minute), or indomethacin (50 microg/100 mL per minute), a cyclooxygenase inhibitor, and by sodium nitroprusside (1, 2, and 4 microg/100 mL per minute), an endothelium-independent vasodilator. Vasodilation to acetylcholine was lower (P<.01) in essential hypertensive patients than normotensive control subjects, and in both groups, it declined with advancing age. In normotensive subjects older than 30 years, L-arginine potentiated the response to acetylcholine in parallel with increasing age, whereas indomethacin increased the vasodilation to acetylcholine only in the oldest group (>60 years). In younger hypertensive patients (<30 years), L-arginine but not indomethacin potentiated the response to acetylcholine. In adult patients (31 to 45 years), L-arginine still potentiated the vasodilation to acetylcholine, and indomethacin began to show some effect. In the oldest patients (46 to 60 and >60 years), L-arginine was no longer effective, and indomethacin exerted a potentiating action that was positively related to advancing age. In normotensive and hypertensive humans, similar mechanisms, including dysfunction of the nitric oxide pathway and production of cyclooxygenase-dependent vasoconstrictors, cause age-related impairment of endothelium-dependent vasodilation, and only their earlier appearance characterizes hypertensive disease. Thus, the endothelial dysfunction that occurs in hypertension seems to represent an accelerated form of dysfunction that occurs in aging.

Acetylcholine↗
PubMed1997

Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients.

Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to test whether antihypertensive treatment with the calcium antagonist lacidipine can improve endothelium-dependent vasodilation in essential hypertensive patients. In 12 normotensive subjects (mean age, 47.8+/-8.6 years; blood pressure, 118.6+/-4.2/76.7+/-3.9 mm Hg) and 19 hypertensive patients (mean age, 49.4+/-10.2 years; blood pressure; 153.5+/-13.3/101.3+/-6.4 mm Hg), we studied forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute) and bradykinin (5, 15, and 50 ng/100 mL per minute), two endothelium-dependent vasodilators that act through different receptors and signal transduction pathways, and sodium nitroprusside (1, 2, and 4 microg/100 mL per minute), an endothelium-independent vasodilator. In essential hypertensive patients, vascular reactivity was repeated during prolonged (8 weeks of oral treatment at 6 mg/d) lacidipine administration and 2 weeks after withdrawal of chronic (32-week) treatment. Hypertensive patients showed significantly (P<.01) blunted vasodilation in response to acetylcholine (vascular resistance, 31.5+/-4.9 to 7.6+/-2.4 SU) and bradykinin (vascular resistance, 32.3+/-5.8 to 8.5+/-3.0 SU) compared with control subjects (vascular resistance: acetylcholine, 24.3+/-3.9 to 3.7+/-1.2 SU; bradykinin, 24.7+/-0.4 to 4.1+/-1.3 SU), whereas the response to sodium nitroprusside was similar. After either 8 or 32 weeks of lacidipine treatment, the vasodilation in response to acetylcholine (30.6+/-7.7 to 5.7+/-1.5 and 34.3+/-6.6 to 5.9+/-1.9 SU, respectively) and bradykinin (31.3+/-7.2 to 6.4+/-1.6 and 33.7+/-5.4 to 6.1+/-1.5 SU, respectively), but not to sodium nitroprusside, proved to be significantly (P<.05) increased compared with baseline. In essential hypertensive patients, oral treatment with lacidipine increased forearm vasodilation in response to acetylcholine and bradykinin, suggesting that this drug can improve endothelial function in patients with essential hypertension.

Acetylcholine↗
PubMed1997

Transcapillary escape rate of albumin in type II diabetic patients. The relationship with microalbuminuria and hypertension.

OBJECTIVE: To study why in type II diabetes, microalbuminuria, a marker of generalized vascular dysfunction, and hypertension have been linked with both renal and cardiovascular organ damage. RESEARCH DESIGN AND METHODS: To investigate the effect of moderately elevated blood pressure on vascular damage, the transcapillary escape rate of albumin (TERalb) was measured by intravenous injection of purified 125I-human serum albumin in 9 healthy control subjects (group 1), 9 nondiabetic hypertensive subjects (group 2), and 73 nonobese type II diabetic patients stratified as follows: group 3: 17 normoalbuminuric-normotensive subjects; group 4: 22 normoalbuminuric-hypertensive subjects (systolic blood pressure [sBP] > or = 140 mmHg or diastolic blood pressure [dBP] > or = mmHg or both); group 5: 16 normotensive subjects with microalbuminuria (albumin excretion rate [AER]: 20-200 micrograms/min); and group 6: 18 microalbuminuric-hypertensive subjects. RESULTS: Groups 3-6 had similar age, sex, duration of diabetes (group 3: 7.8 +/- 5.5; group 4: 9.7 +/- 8.7; group 5: 12.1 +/- 8.1; and group 6: 10.7 +/- 8.3 years), BMI, HbA1c (7.8 +/- 1.1, 7.5 +/- 1.5, 8.7 +/- 1.5, and 7.7 +/- 1.1%, respectively), blood glucose, and lipid profile. Systolic and diastolic blood pressure did not differ in the three hypertensive group (group 2: 154 +/- 3/99 +/- 6; group 4: 149 +/- 13/95 +/- 6; group 6: 154 +/- 15/91 +/- 9 mmHg) and were significantly lower (P < 0.001) in group 3 (126 +/- 12/76 +/- 7), group 5 (128 +/- 11/77 +/- 5), and healthy control subjects (group 1: 133 +/- 7/81 +/- 4). TERalb was similar in control subjects (5.77 +/- 1.06%/h) and in normoalbuminuric-normotensive subjects (5.81 +/- 1.51%/h) but significantly higher (P < 0.0001) in microalbuminuric subjects with or without hypertension (9.11 +/- 1.65 and 8.60 +/- 1.50%/h, respectively) as well as in normoalbuminuric diabetic patients with hypertension (8.10 +/- 2.27%/h) and in essential hypertensive subjects (8.12 +/- 1.68%/h). CONCLUSIONS: By stepwise regression, TERalb was related (step 1) to log-AER (r = 0.30) or to the presence of microalbuminuria (r = 0.36) and (step 2) to dBP (multiple r = 0.40) or to the presence of hypertension (multiple r = 0.51) in the whole diabetic cohort (groups 3-6). TERalb was related to dBP (r = 0.47) or to the presence of hypertension (r = 0.56) only in normoalbuminuric diabetic patients (groups 3 and 4) and to log-AER (r = 0.56) or the presence of microalbuminuria (r = 0.68) only in normotensive patients (groups 3 and 5). In type II diabetic patients, TERalb was elevated in subjects with increased albuminuria, irrespective of blood pressure levels, but also was independently related to the presence of mild-to-moderate systemic hypertension.

Adult↗
PubMed1996

Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients.

BACKGROUND: Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to investigate whether this abnormality is a primary defect or a consequence of blood pressure increases. METHODS AND RESULTS: In offspring of essential hypertensive patients (n = 34) and normotensive subjects (n = 30), we evaluated forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator. Minimal forearm vascular resistances also were calculated as the ratio between mean intra-arterial pressure and maximal forearm blood flow induced by forearm ischemia and hand exercise. Vasodilation to acetylcholine was significantly (P < .01) blunted in offspring of hypertensive patients compared with offspring of normotensive subjects, whereas the responses to sodium nitroprusside and minimal forearm vascular resistances were similar. In two subgroups of 14 offspring of essential hypertensive patients but not in 10 offspring of normotensive subjects, vasodilation to acetylcholine was increased by intra-brachial L-arginine (1 mumol.100 mL-1.min-1), the substrate for nitric oxide synthesis, whereas in the other 10 and 8 offspring of essential hypertensive patients and normotensive subjects, respectively, cyclooxygenase blockade by intra-brachial indomethacin (50 micrograms.100 mL-1.min-1) was ineffective. CONCLUSIONS: Offspring of essential hypertensive patients are characterized by a reduced response to acetylcholine linked to a defect in the nitric oxide pathway, suggesting that an impairment in nitric oxide production precedes the onset of essential hypertension.

Acetylcholine↗
PubMed1996

Presence of cardiovascular structural changes in essential hypertensive patients with coronary microvascular disease and effects of long-term treatment.

In asymptomatic essential hypertensive patients with angiographically normal coronary arteries and without left ventricular hypertrophy, dipyridamole-induced ischemic-like ST segment depression may be a marker of coronary microvascular disease. In this study we evaluated, first, whether this cardiac abnormality is linked to structural or functional vascular abnormalities, and second, the effect of antihypertensive treatment by 12-month administration of the angiotensin converting enzyme (ACE) inhibitor captopril (50 mg twice a day orally). In essential hypertensives with dipypridamole echocardiography stress test (DET) (DET+, n = 8) and without (DET-, n = 8) ST segment depression greater than 0.1 mV during intravenous dipyridamole infusion (0.84 mg/kg over 10 min), we studied the forearm blood flow (FBF, venous plethysmography, mL/100) modifications induced by intrabrachial acetylcholine (Ach) (0.15, 0.45, 1.5, 4.5, 15 micrograms/100 mL/min x 5 min each), an endothelium-dependent vasodilator, and by sodium nitroprusside (SNP) (1, 2, 4 micrograms/100 mL/min x 5 min each), a smooth muscle cell relaxant compound. Minimal forearm vascular resistances (MFVR), an index of arteriolar structural changes, were also calculated. Both Ach and SNP caused greater vasodilation in DET- as compared to DET+ while MFVRs were lower in DET- compared to DET+. After treatment, both DET+ and DET- patients showed a significant and similar reduction in blood pressure and left ventricular mass index, while vasodilation to acetylcholine and sodium nitroprusside was increased only in the DET+ group. In addition, forearm minimal vascular resistances were significantly reduced only in DET+ patients, who showed disappearance of dipyridamole-induced ischemic-like ST segment depression. In conclusion, these data confirm that essential hypertensive patients with microvascular coronary disease are characterized by the presence of structural changes in the forearm vascular bed. Our results also indicate that both cardiac and forearm vascular abnormalities can be reversed by antihypertensive treatment with an ACE inhibitor.

Acetylcholine↗
PubMed1996

Renovascular hypertension and insulin sensitivity.

We tested the hypothesis that the status of the renin-angiotensin-aldosterone system affects insulin sensitivity. Insulin sensitivity (by the euglycaemic insulin clamp technique) was measured in eight patients with angiographically proven renovascular hypertension and in eight normotensive subjects matched for age, gender, body mass index and glucose tolerance. In the patients, insulin sensitivity was measured both at baseline and following 7 days of ACE inhibition. Following glucose ingestion, patients and controls showed similar insulin and glucose responses. Insulin infusion (7 pmol min-1 kg-1) promoted similar glucose utilization in the hypertensives and normotensives: 24.8 +/- 2.3 vs. 26.0 +/- 3.0 mumol min-1 kg-1 respectively. One week of ACE inhibition caused a 20 +/- 4 mmHg decrease in mean blood pressure and a 20 +/- 6% decrease in peripheral vascular resistance. Plasma angiotensin II concentrations dropped from 24.6 +/- 6.3 to 13.5 +/-5.0 pg mL-1 (P < 0.05) and plasma aldosterone from 17 +/- 4 to 9 +/- 2 ng dL-1 (P < 0.05), and plasma renin activity doubled (from 1.6 +/- 0.3 to 3.4 +/- 1.7 ng mL-1 h-1, P < 0.02). Nevertheless, insulin sensitivity was unchanged (before, 24.8 +/- 2.3; after 25.8 +/- 2.2 mumol min-1 kg-1, P = Ns). During insulin infusion, forearm blood flow did not change from baseline in either set of studies. Also, the antinatriuretic (before, -26 +/- 18; after, -22 +/- 14%) and antikaliuretic (before: -36 +/- 13%, after -39 +/- 11%) action of the hormone was unaffected by the therapy. In conclusion, renovascular hypertension is not associated with insulin resistance. Furthermore, a selective, drastic reduction of the renin-angiotensin-aldosterone system activity and vascular tone does not alter insulin action on glucose and electrolyte metabolism.

Adult↗
PubMed1996

Trough:peak ratio of nifedipine gastrointestinal therapeutic system and nifedipine retard in essential hypertensive patients: an Italian multicentre study.

OBJECTIVE: To evaluate the antihypertensive effect of nifedipine gastrointestinal therapeutic system and retard in terms of trough:peak ratio efficacy. METHODS: According to a double-blind, randomized, crossover design, 58 patients with mild-to-moderate essential hypertension, after 1 month placebo washout, received 30 mg/day nifedipine gastrointestinal therapeutic system, 20 mg nifedipine retard twice a day and the corresponding placebos for 1 month. At the end of each treatment period, blood pressure was measured by using a mercury sphygmomanometer at trough and 1, 2, 3 and 4 h after the last dosing. The peak effect was identified as the maximum decrement induced by the three randomized treatments with respect to the value at the end of the placebo washout period during the 4 h interval. The trough:peak ratios of systolic and diastolic blood pressure were calculated as group ratios and individual ratios from decrements induced by nifedipine gastrointestinal therapeutic system and retard, corrected for those induced by randomized placebo. Patients were defined as responders to each randomized treatment if their diastolic blood pressure at trough time was reduced by at least 10 mmHg relative to that at the corresponding time at the end of placebo washout. RESULTS: Nifedipine gastrointestinal therapeutic system and retard significantly reduced blood pressure to a similar extent both at trough and at peak. Systolic and diastolic group trough:peak ratios in responders to nifedipine gastrointestinal therapeutic system (n = 41) were 0.80 and 0.88, respectively, and those in responders to nifedipine retard (n = 30) 0.84 and 0.93, respectively. The percentage of patients with trough:peak ratios > 0.50 was > 80% (systolic trough:peak ratios) and above 90% (diastolic trough: peak ratios) for both nifedipine formulations. CONCLUSIONS: Our data show that 30 mg/day nifedipine gastrointestinal therapeutic system and 20 mg nifedipine retard twice a day have a favourable trough:peak ratios efficacy when given as monotherapy to essential hypertensive patients.

Adult↗
PubMed1996

Rilmenidine activates postjunctional alpha 1- and alpha 2-adrenoceptors in the canine saphenous vein.

Experiments were performed to determine the subtypes of alpha-adrenoceptors involved in the contraction induced by rilmenidine in isolated canine cutaneous veins. Rings of saphenous vein (without endothelium) were suspended for the recording of isometric force in physiological salt solution. All experiments were performed in the presence of propranolol (to antagonize beta-adrenoceptors), cocaine (to inhibit neuronal uptake) and hydrocortisone (to inhibit extraneuronal uptake). In the presence of rauwolscine (an alpha 2-adrenergic blocker), rilmenidine caused concentration-dependent contractions which were inhibited by prazosin (nonselective alpha 1-antagonist) and by (+)niguldipine (selective alpha 1A-adrenergic antagonist), but not by (-)niguldipine. After treatment with phenoxybenzamine (to alkylate alpha 1-adrenoceptors), rilmenidine evoked contractions of the canine saphenous vein which were antagonized competitively by rauwolscine. The combination of rauwolscine and prazosin did not abolish contractions evoked by the highest concentrations of rilmenidine. Although binding experiments using 3H-idazoxan suggested the existence of a nonadrenergic binding site (around 20% of the total binding), contractile studies failed to demonstrate their involvement in the increases in tension evoked by rilmenidine. These experiments suggest that the contractions evoked by rilmenidine in isolated canine veins are mediated by both alpha 1A- and alpha 2-adrenoceptors.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1996

Menopause is associated with endothelial dysfunction in women.

To evaluate the effect of endogenous estrogens on endothelial function in humans, we examined whether menopause is associated with impairment in endothelium-dependent vasodilation in normotensive and essential hypertensive women. In 73 normotensive subjects (37 women, 36 men) and 73 hypertensive patients (36 women, 37 men), we studied endothelial function by measuring forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1,2, and 4 micrograms/100 mL per minute), an endothelium-independent vasodilator. Women younger than 45 years had normal menstrual cycles. In essential hypertensive patients, responses to acetylcholine but not to sodium nitroprusside were significantly (P < .001) reduced compared with responses in normotensive subjects. Moreover, in both groups, vasodilation to acetylcholine showed a marked negative correlation with advancing age (normotensive subjects: r = -.88, P < .001; hypertensive patients: r = -.87, P < .001). In contrast, vasodilation to sodium nitroprusside showed a less evident negative correlation with advancing age (normotensive subjects: r = -46, P < .01; hypertensive patients: r = -.48, P < .01). However, in normally menstruating normotensive women, no endothelial dysfunction was observed, and age-related impairment in endothelium-dependent vasodilation was evident only after menopause. In normally menstruating hypertensive women, aging was associated with endothelial dysfunction although the deterioration of endothelium-dependent vasodilation was less marked than that in men. In contrast, after menopause, the age-related endothelial dysfunction in hypertensive women was similar to that observed in men. Finally, no sex-related difference in the response to sodium nitroprusside was observed in either normotensive subjects or essential hypertensive patients. Age-related endothelial dysfunction is attenuated in premenopausal normotensive and hypertensive women compared with men, whereas no sex-induced difference is observed after menopause, suggesting a protective effect of endogenous estrogens on endothelial function.

Acetylcholine↗
PubMed1996

Cardiovascular characteristics in normotensive subjects with or without family history of hypertension.

The aim of our study was to evaluate whether initial changes of cardiovascular structure and/or function can be detected in young normotensive subjects with (F+) and without (F-) family history of hypertension. Thirty-two subjects (19 F+, 10 males and 9 females, age range 17-32 years; 13 F-, 6 males and 7 females, age range 19-33 years) were studied. In each subject 24 hours ambulatory blood pressure monitoring, a M-mode, 2d guided and pulsed doppler echocardiogram and postischemic forearm strain gauge plethysmography were performed. The two groups of subjects did not differ for causal systolic and diastolic BP and 24 hours systolic and diastolic ambulatory monitored blood pressure. No differences in LV end-diastolic and end-systolic diameters, as well as in LV wall thickness, and in LV mass index were observed. Systolic functional parameters were also similar in the two groups. In F+ subjects peak early filling velocity was reduced in respect to F- (p < 0.01), peak late filling velocity integral was increased (p < 0.05) and the ratio of peak E/peak A integrals was decreased (p < 0.05). No difference was observed for postischemic forearm blood flow and minimal vascular resistance, taken as an index of arteriolar structural changes as well as intima-media thickness of carotid arteries. In conclusion in this study F+ and F- had similar BP values, LV mass and min VR; differences previously observed in LV mass between F+ and F- may have been due to the presence of different basal levels of BP; in F+ LV diastolic filling, although still in the normal range, shifted early toward the pattern of LV filling usually observed in hypertensive patients.

Adult↗
PubMed1995

Effect of insulin on acetylcholine-induced vasodilation in normotensive subjects and patients with essential hypertension.

BACKGROUND: The present study was designed to directly test the vasodilation action of insulin and its relation to endothelium-dependent mechanisms. METHODS AND RESULTS: In 18 normotensive subjects and 27 patients with untreated mild to moderate essential hypertension, we studied the effect of intrabrachial insulin on the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (at doses of 0.15, 0.45, 1.5, 4.5, and 15 micrograms.min-1.dL-1), an endothelium-dependent vasodilator, or sodium nitroprusside (at doses of 1, 2, and 4 micrograms.min-1.dL-1), and endothelium-independent vasodilator. Local hyperinsulinemia (deep venous plasma insulin, 48 +/- 6 and 51 +/- 5 microU/mL in control subjects and hypertensive patients, respectively) did not affect basal forearm blood flow and stimulated forearm glucose extraction (control subjects, 3 +/- 1% to 11 +/- 2%, P < .001; hypertensive patients, 3 +/- 1% to 6 +/- 1%, P < .001; P < .01 for the between-group difference). In both normotensive and hypertensive subjects, insulin significantly potentiated acetylcholine-induced vasodilation, whereas it did not alter the vasodilatory response to sodium nitroprusside. NG-monomethyl-L-arginine, an inhibitor of endothelial nitric oxide synthesis, blunted insulin-induced facilitation of acetylcholine vasodilation in normotensive but not in hypertensive subjects. In contrast, in hypertensive patients but not in normotensive control subjects, the potentiation of the vascular response to acetylcholine induced by local hyperinsulinemia was abolished by intrabrachial ouabain, an inhibitor of Na(+)-K+ pump. CONCLUSIONS: In healthy humans and essential hypertensive patients alike, local physiological hyperinsulinemia per se does not increase forearm blood flow but potentiates the vasodilation induced by acetylcholine regardless of metabolic insulin resistance. This effect is endothelium-dependent because it is not seen with nitroprusside and is related to the L-arginine-nitric oxide pathway in normotensive subjects and to smooth muscle cell hyperpolarization in essential hypertensive patients.

Acetylcholine↗