Biomedical subjects

C Cardillo

Publications and source records attributed to C Cardillo.

At least 19 recordsLinked to original sources

PubMed2000

Increased activity of endogenous endothelin in patients with hypercholesterolemia.

OBJECTIVE: We sought to assess the activity of endogenous endothelin-1 (ET-1) in hypercholesterolemic patients using antagonists of ET-1 receptors. BACKGROUND: Endothelial dysfunction in hypercholesterolemic patients may contribute to their risk of premature atherosclerosis. Endothelin, a peptide released by endothelial cells, may be involved in this process by activating smooth muscle cell mitogenesis and leukocyte adhesion. METHODS: Forearm blood flow (FBF) responses (strain-gauge plethysmography) to intra-arterial infusion of a selective blocker of ETA receptors (BQ-123) and, on a separate occasion, to ET-1 were measured in 12 hypercholesterolemic patients and 12 normal control subjects. In addition, on a different day, six hypercholesterolemic patients received co-infusion of BQ- 123 and BQ-788 (a selective blocker of ETB receptors). RESULTS: In normal subjects, BQ-123 did not significantly modify FBF from baseline (p = 0.78); however, in hypercholesterolemic patients, BQ-123 administration resulted in a significant vasodilator response (p < 0.001). Administration of exogenous ET-1 resulted in similar vasoconstrictor responses in patients (37%) and control subjects (35%) (p = 0.83). In hypercholesterolemic patients, the vasodilator response to selective ETA blockade was reversed by nonselective blockade of ET-1 receptors obtained by co-infusion of BQ-123 and BQ-788. CONCLUSIONS: The vascular activity of endogenous ET-1 is enhanced in hypercholesterolemic patients, whereas their sensitivity to exogenous ET-1 is unchanged. These findings suggest increased production of ET-1, which may participate in the pathophysiology of vascular disease characteristic of hypercholesterolemia.

Endothelin Receptor Antagonists↗

PubMed2000

Interactions between nitric oxide and endothelin in the regulation of vascular tone of human resistance vessels in vivo.

Endothelial release of nitric oxide (NO) contributes to the regulation of vascular tone by inducing vascular relaxation. In addition, NO may inhibit the synthesis and hemodynamic effects of endothelin-1 (ET-1), a powerful endothelium-derived vasoconstrictor peptide that may stimulate NO production. However, whether NO and ET-1 physiologically interact to regulate vascular tone in humans has not been defined. In this study, the interactions between the L-arginine NO pathway and the ET-1 system in the regulation of vascular tone in human forearm resistance vessels were examined in vivo. Vasomotor response to the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 4 micromol/min for 30 minutes) was measured during either saline infusion or blockade of ET-1 receptors. Endothelin-A (ET(A)) and endothelin-B (ET(B)) receptor blockade was achieved by infusion of BQ-123 (100 nmol/min) and BQ-788 (50 nmol/min), respectively, separately and in combination. Drugs were infused into the brachial artery, and the forearm blood flow (FBF) response was measured by strain-gauge plethysmography. During saline infusion, L-NMMA administration significantly decreased FBF (25%, P<0.01 versus baseline). This effect was significantly blunted during nonselective blockade of ET-1 receptors (7% decrease in FBF, P=0.02 versus the effect of L-NMMA during saline infusion). Selective ET(A) blockade did not modify the vasoconstrictor response to L-NMMA (26% decrease in FBF, P=0.66 versus the effect of L-NMMA during saline infusion), but selective ET(B) receptor antagonism caused significant diminution of the hemodynamic response to NO inhibition (8% decrease in FBF, P=0.04 versus the effect of L-NMMA during saline infusion). Thus ET-1 contributes to the regulation of vascular tone by stimulating NO activity. This effect is mediated through endothelial ET(B) receptors and may be relevant in conditions associated with endothelial dysfunction.

Endothelin Receptor Antagonists↗

PubMed1999

Insulin stimulates both endothelin and nitric oxide activity in the human forearm.

BACKGROUND: The mechanism of the hemodynamic effect of insulin in the skeletal muscle circulation has not been fully elucidated. The purpose of this study was to assess whether the hemodynamic response to insulin involves the concurrent release of endothelin (ET-1) and nitric oxide (NO), 2 substances with opposing vasoactive properties. METHODS AND RESULTS: Bioactivity of ET-1 and NO was assessed without insulin and during insulin infusion in the forearm circulation of healthy subjects by use of blockers of ET-1 receptors and by NO synthesis inhibition. In the absence of hyperinsulinemia, ET-1 receptor blockade did not result in any significant change in forearm blood flow from baseline (P=0.29). Intra-arterial insulin administration did not significantly modify forearm blood flow (P=0. 88). However, in the presence of hyperinsulinemia, ET-1 receptor antagonism was associated with a significant vasodilator response (P<0.001). In the presence of ET-1 receptor blockade, the vasoconstrictor response to NO inhibition by N(G)-monomethyl-L-arginine was significantly higher after insulin infusion than in the absence of hyperinsulinemia (P=0.006). CONCLUSIONS: These findings suggest that in the skeletal muscle circulation, insulin stimulates both ET-1 and NO activity. An imbalance between the release of these 2 substances may be involved in the pathophysiology of hypertension and atherosclerosis in insulin-resistant states associated with endothelial dysfunction.

Endothelin-1↗

PubMed1999

Vascular effects of estrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women.

BACKGROUND: Lipoproteins affect endothelium-dependent vasomotor responsiveness. Because lipoprotein effects of estrogen and cholesterol-lowering therapies differ, we studied the vascular responses to these therapies in hypercholesterolemic postmenopausal women. METHODS AND RESULTS: We randomly assigned 28 women to conjugated equine estrogen (CE) 0.625 mg, simvastatin 10 mg, and their combination daily for 6 weeks. Compared with respective baseline values, simvastatin alone and combined with CE reduced LDL cholesterol to a greater extent than CE alone (both P<0.05). CE alone and combined with simvastatin raised HDL cholesterol and lowered lipoprotein(a) to a greater extent than simvastatin alone (all P<0.05). Flow-mediated dilation of the brachial artery (by ultrasonography) improved (all P<0.001 versus baseline values) on CE (4.0+/-2.6% to 10.2+/-3.9%), simvastatin (4.3+/-2.4% to 10.0+/-3.9%), and CE combined with simvastatin (4.6+/-2.0% to 9.8+/-2.6%), but similarly among therapies (P=0.507 by ANOVA). None of the therapies improved the dilator response to nitroglycerin (all P>/=0.184). Only therapies including CE lowered levels of plasminogen activator inhibitor type 1 and the cell adhesion molecule E-selectin (all P<0. 05 versus simvastatin). CONCLUSIONS: Although estrogen and statin therapies have differing effects on lipoprotein levels, specific improvement in endothelium-dependent vasodilator responsiveness is similar. However, only therapies including estrogen improved markers of fibrinolysis and vascular inflammation. Thus, estrogen therapy appears to have unique properties that may benefit the vasculature of hypercholesterolemic postmenopausal women, even if they are already on cholesterol-lowering therapy.

Aged↗

PubMed1999

No cardiovascular effects of single-dose pseudoephedrine in patients with essential hypertension treated with beta-blockers.

OBJECTIVE: The use of the decongestant pseudoephedrine has been cautioned in patients with arterial hypertension, due to the possible rise in blood pressure induced by the sympathostimulatory properties of the drug. This effect could be enhanced in hypertensives treated with beta-blockers, in whom the vasoconstrictor effect of alpha-adrenergic stimulation is unbalanced. The purpose of this study was to investigate the cardiovascular response to pseudoephedrine in hypertensive patients treated with different types of beta-blockers. METHODS: We recruited 29 (18 males) mild-to-moderate essential hypertensive patients [mean age 49(2) years] in a randomized, placebo-controlled, crossover trial. All participants received either placebo, or a nonselective (propranolol 160 mg once daily) or a selective (atenolol 100 mg once daily) beta-blocker for 1 week. At the end of each period, all patients received a single oral dose of pseudoephedrine (60 mg) and their blood pressure and heart rate were monitored at repeated intervals for 2 h. RESULTS: After 1 week of propranolol or atenolol, patients had significantly lower systolic blood pressure and heart rate than after placebo, whereas diastolic blood pressure was not significantly modified. The acute administration of pseudoephedrine did not change systolic and diastolic blood pressure and heart rate from baseline at the end of any of the treatment periods. CONCLUSIONS: A standard oral dose of pseudoephedrine does not significantly affect blood pressure values in hypertensive patients treated with beta-blockers, and therefore may be safely used in this subset of patients.

Adrenergic alpha-Agonists↗

PubMed1999

Role of endothelin in the increased vascular tone of patients with essential hypertension.

We investigated the possible role of endothelin in the increased vasoconstrictor tone of hypertensive patients using antagonists of endothelin receptors. Forearm blood flow (FBF) responses (strain-gauge plethysmography) to intraarterial infusion of blockers of endothelin-A (ETA) (BQ-123) and endothelin-B (ETB) (BQ-788) receptors, separately and in combination, were measured in hypertensive patients and normotensive control subjects. In healthy subjects, BQ-123 alone or in combination with BQ-788 did not significantly modify FBF (P=0.78 and P=0.63, respectively). In hypertensive patients, in contrast, BQ-123 increased FBF by 33+/-7% (P<0.001 versus baseline), and the combination of BQ-123 and BQ-788 resulted in a greater vasodilator response (63+/-12%; P=0.006 versus BQ-123 alone in the same subjects). BQ-788 produced a divergent vasoactive effect in the two groups, with a decrease of FBF (17+/-5%; P=0.004 versus baseline) in control subjects and transient vasodilation (15+/-7% after 20 minutes) in hypertensive patients (P<0.001, hypertensives versus controls). The vasoconstrictor response to endothelin-1 was slightly higher (P=0.04) in hypertensive patients (46+/-4%) than in control subjects (32+/-4%). Our data indicate that patients with essential hypertension have increased vascular endothelin activity, which may be of pathophysiological relevance to their increased vascular tone. In these patients, nonselective ETA and ETB blockade seems to produce a greater vasodilator effect than selective ETA blockade.

Endothelin-1↗

PubMed1998

Selective defect in nitric oxide synthesis may explain the impaired endothelium-dependent vasodilation in patients with essential hypertension.

BACKGROUND: Patients with essential hypertension have impaired endothelial NO activity, but the mechanism underlying this abnormality is unknown. METHODS AND RESULTS: To investigate whether the endothelial dysfunction of hypertensive patients is related to a selective defect in NO synthesis, we studied the forearm blood flow responses to intra-arterial infusion of acetylcholine (7.5 to 30 microg/min), an endothelial agonist linked to NO synthase through the Ca2+ signaling pathway, and isoproterenol (50 to 200 ng/min), a beta-adrenoceptor agonist that stimulates NO production by increasing intracellular cAMP, in 12 normotensive subjects and 12 hypertensive patients. The infusion of isoproterenol was repeated during the concurrent blockade of NO synthesis by NG-monomethyl-L-arginine (L-NMMA; 4 micromol/min). The vasodilator response to acetylcholine was significantly reduced in hypertensives compared with normotensives (maximum blood flow: 10.4+/-4.6 versus 14.4+/-3.7 mL x min[-1] x dL[-1]; P=.008). However, the vasodilator effect of isoproterenol was similar in normotensives and hypertensives (maximum blood flow: 14.4+/-5.4 versus 13.5+/-5 mL x min[-1] x dL[-1]; P=.56) and was significantly (both P<.01) and equally blunted by L-NMMA in both groups (maximum blood flow: 11+/-3 mL x min[-1] x dL[-1] in normotensives versus 10.8+/-3.9 mL x min[-1] x dL[-1] in hypertensives; P=.77). The vasodilator response to sodium nitroprusside (0.8 to 3.2 microg/min), an exogenous NO donor, was similar in both groups and was not modified by L-NMMA. CONCLUSIONS: Hypertensive patients have impaired endothelium-dependent vasodilation in response to acetylcholine but preserved NO activity in response to beta-adrenergic stimulation. These findings suggest that the endothelial dysfunction in essential hypertension is due to a selective abnormality of NO synthesis, probably related to a defect in the phosphatidylinositol/Ca2+ signaling pathway.

Acetylcholine↗

PubMed1998

Impairment of the nitric oxide-mediated vasodilator response to mental stress in hypertensive but not in hypercholesterolemic patients.

OBJECTIVES: This study investigated whether mental stress-induced vasodilation mediated by endothelium-derived nitric oxide (NO) is defective in conditions with endothelial dysfunction, such as hypertension and hypercholesterolemia. BACKGROUND: Vascular release of NO modulates the vasodilator response to mental stress in healthy subjects. Previous studies have shown that hypertensive and hypercholesterolemic patients have impaired endothelium-dependent vasodilation to pharmacologic agents due to decreased NO activity. However, whether this abnormality also operates in response to physiologic stimuli such as mental stress has not been defined. METHODS: Forearm blood flow responses (plethysmography) to mental stress were compared in 12 normal subjects, 12 hypertensive patients and 10 hypercholesterolemic patients before and during NO synthesis inhibition with N(G)-monomethyl-L-arginine (4 micromol/min). Vascular responses to acetylcholine (7.5, 15 and 30 microg/min), an endothelium-dependent vasodilator, and sodium nitroprusside (0.8, 1.6 and 3.2 microg/min), an exogenous NO donor, were also assessed in each group. RESULTS: During saline the vasodilator response to mental stress was significantly blunted in hypertensive (37+/-11%; p=0.01) but not in hypercholesterolemic (85+/-21%; p=0.78) patients compared with controls (93+/-15%). N(G)-Monomethyl-L-arginine administration significantly blunted mental stress-induced vasodilation in healthy subjects (p=0.004 vs. saline) and hypercholesterolemic patients (p=0.03 vs. saline), but not in hypertensive patients (p=0.69 vs. saline). The vasodilator effect of the highest dose of acetylcholine was similarly blunted in hypertensive (215+/-44%; p=0.02) and hypercholesterolemic (172+/-71%; p=0.02) patients compared with controls (364+/-34), whereas the vasorelaxing response to sodium nitroprusside was similar in the three groups. CONCLUSIONS: Hypertensive but not hypercholesterolemic patients have impaired NO-dependent vasodilation during mental stress. These findings may be accounted for by different mechanisms underlying endothelial dysfunction in these two conditions and might explain an increased susceptibility of hypertensive patients to vascular damage over repeated exposure to stressful situations.

Acetylcholine↗

PubMed1998

Racial differences in nitric oxide-mediated vasodilator response to mental stress in the forearm circulation.

An abnormal hemodynamic response to stressful stimuli has been proposed as a mechanism involved in the higher prevalence of hypertension in blacks. Given the important role of nitric oxide (NO) in the regulation of cardiovascular homeostasis, we investigated the possibility of racial differences in vascular NO activity during mental stress. To test this hypothesis, we compared the forearm blood flow (FBF) response to mental stress in 14 white and 12 black healthy subjects during intra-arterial infusion of either saline or NO synthesis inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 4 micromol/min). We also examined vascular responses of the two groups to intra-arterial infusion of sodium nitroprusside (0.8 to 3.2 microg/min), an exogenous NO donor. During saline infusion, the increase in FBF from baseline induced by mental stress was significantly higher in whites than in blacks (109+/-20% versus 58+/-8%; P=0.03). L-NMMA significantly reduced stress-induced increase in FBF in whites (from 109+/-20% to 54+/-11%; P=0.004) but not in blacks (from 58+/-8% to 42+/-10%; P=0.24); thus, the vasodilator effect of stress testing during L-NMMA was similar in whites and blacks (54+/-11% versus 42+/-10%; P=0.44). The vasodilator response to sodium nitroprusside was also lower in blacks than in whites (maximum flow, 6.9+/-2 versus 11.6+/-3.5 mL x min(-1) x dL(-1); P=0.001) and was not significantly modified by L-NMMA in either group. Our findings indicate that blacks have a reduced NO-dependent vasodilator activity during mental stress. This difference seems related to reduced sensitivity of smooth muscle to the vasodilator effect of NO and may play some role in the increased prevalence of hypertension and its complications in blacks.

Adult↗

PubMed1998

Vasodilator response to systemic but not to local hyperinsulinemia in the human forearm.

Insulin-mediated vasodilation has been proposed as an important determinant of whole-body insulin-stimulated glucose disposal. However, it is not clear whether the vasodilator effect of insulin results from a direct action of the hormone or whether alternative mechanisms are involved. To better characterize the mechanism of insulin-mediated vasorelaxation, we compared forearm blood flow (FBF) responses to local (intra-arterial) and systemic (intravenous, euglycemic clamp) hyperinsulinemia in 10 healthy lean subjects using venous occlusion plethysmography. In addition, we assessed the effect of nitric oxide (NO) synthase inhibition by NG-monomethyl-L-arginine (L-NMMA) on the vasodilator and metabolic responses to hyperinsulinemia. Similar forearm concentrations of insulin were achieved during local and systemic infusion (231+/-39 versus 265+/-22 microU/mL; P=0.54). Of note, FBF did not change significantly in response to local hyperinsulinemia (from 2.6+/-0.3 to 2.4+/-0.3 mL . min-1 . dL-1; P=0.50). In contrast, systemic hyperinsulinemia caused a 52% increase in FBF (from 2.5+/-0.2 to 3. 8+/-0.5 mL . min-1 . dL-1; P<0.004), which was reversed by L-NMMA (FBF decreased from 3.8+/-0.5 to 2.3+/-0.2 mL . min-1 . dL-1; P=0. 004). We conclude that systemic, but not local, hyperinsulinemia induces vasodilation in the forearm. Our findings suggest that insulin-mediated vasodilation is not due solely to a direct stimulatory effect of insulin but involves additional mechanisms activated only during systemic hyperinsulinemia.

Female↗

PubMed1998

Impaired endothelial regulation of vascular tone in patients with systemic arterial hypertension.

The discovery of the endothelium as a major regulator of vascular tone triggered intense research among basic and clinical investigators to unravel the physiologic and pathophysiologic significance of this phenomenon. Importantly, endothelial modulation of the contractile state of vascular smooth muscle has been shown to be impaired in atherosclerosis and in several conditions known to be associated with the premature development of atherosclerosis. Studies in several different animal models of arterial hypertension, and in patients with both essential and secondary hypertension, have demonstrated an association between elevated systemic blood pressure and impaired endothelium-dependent vascular relaxation. More recently, a diminished bioavailability of nitric oxide (NO) has been identified as a mechanism responsible for endothelial dysfunction in hypertensive patients. Different processes may, in turn, explain this decreased vascular activity of NO. The present review focuses on those clinical studies that are aimed at identifying the precise abnormality responsible for reduced NO-dependent vasodilation in patients with essential hypertension. Understanding of the basic mechanisms of this process may prove to be beneficial for the development of more specific therapies and ultimately for the outcome of hypertensive patients.

Animals↗

PubMed1997

Role of nitric oxide in the vasodilator response to mental stress in normal subjects.

Vascular production of nitric oxide (NO) plays an important role in a variety of physiologic processes. This study examines the contribution of NO to the vasodilator response to mental stress. The effects of mental arithmetic testing on forearm vascular dynamics were analyzed in 15 normal subjects (9 men; age 45 +/- 12 years) during intraarterial infusion of either saline or N(G)-monomethyl-L-arginine (L-NMMA; 4 micromol/min for 15 minutes), an inhibitor of NO synthesis. The effect of L-NMMA on endothelium-independent vasodilation induced by intraarterial infusion of sodium nitroprusside was also studied in 11 of the 15 subjects. Forearm blood flow was measured by plethysmography. Mental stress increased forearm blood flow from 2.35 +/- 0.84 to 5.06 +/- 2.66 ml/min/dl (115%) during saline and from 1.72 +/- 0.59 to 2.81 +/- 0.99 ml/min/dl (63%) during L-NMMA infusion. The vasodilator effect of mental stress was significantly lower during L-NMMA infusion than during saline (1.1 +/- 0.65 vs 2.71 +/- 2.15 ml/min/dl; p = 0.01). L-NMMA administration did not significantly change mean arterial pressure and heart rate responses to mental stress. In contrast, the vasodilator effect of sodium nitroprusside (1.6 microg/min) was similar during infusion of L-NMMA and during saline (3.75 +/- 1.55 vs 2.85 +/- 1.38 ml/min/dl; p = 0.16). These findings indicate that local release of NO is involved in the forearm vasodilator response to mental stress.

Adult↗

PubMed1997

Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator function in hypercholesterolemic but not in hypertensive patients.

Hypercholesterolemic and hypertensive patients have impaired endothelium-dependent vasorelaxation because of decreased nitric oxide activity, but the mechanism underlying this abnormality is unknown. This study sought to determine whether an increased breakdown of nitric oxide by xanthine oxidase-generated superoxide anions could participate in these forms of endothelial dysfunction. We studied vascular responses to intrabrachial infusion of acetylcholine (an endothelium-dependent vasodilator, 7.5 to 30 microg/min) and sodium nitroprusside (a direct smooth muscle dilator, 0.8 to 3.2 microg/min) by strain-gauge plethysmography before and during the combined administration of oxypurinol (300 microg/min), a xanthine oxidase inhibitor, in 20 hypercholesterolemic patients, 20 essential hypertensive patients, and 20 normal subjects. The vasodilator response to acetylcholine was blunted in hypercholesterolemic (highest flow, 8.2+/-8 mL x min(-1) x dL(-1)) and hypertensive (8.5+/-4 mL x min(-1) x dL(-1)) patients compared with control subjects (13.8+/- 6.6 mL x min(-1) x dL(-1)) (both P<.001); however, no differences were observed in the response to sodium nitroprusside. Oxypurinol did not change the response to acetylcholine in control subjects (P=.26) and improved, but did not normalize, its vasodilator effect in hypercholesterolemic patients (P<.01). Oxypurinol did not affect the response to acetylcholine in hypertensive patients (P=.34) and did not modify the response to sodium nitroprusside in any group. These results suggest that xanthine oxidase-generated superoxide anions are partly responsible for the impaired endothelial vasodilator function of hypercholesterolemic patients. In contrast, this mechanism does not appear to play a significant role in essential hypertension.

Acetylcholine↗

PubMed1997

Decreased vasodilator response to isoproterenol during nitric oxide inhibition in humans.

The vasodilator effect of beta-adrenergic agonists has traditionally been ascribed solely to a direct effect on vascular smooth muscle. Experimental studies, however, have suggested a role of endothelium-derived nitric oxide (NO) in beta-adrenergic-mediated vasodilation. The purpose of this investigation was to determine whether NO contributes to the vasodilator effect of beta-adrenergic stimulation in humans. We analyzed the forearm blood flow response to increasing doses of isoproterenol (50, 100, and 200 ng/min), a beta-adrenoceptor agonist, during the concomitant infusion of saline or N(G)-monomethylL-arginine (L-NMMA; 4 micromol/min), a blocker of NO synthesis, in 23 normal subjects (9 men and 14 women, aged 48 +/- 7 years). The effect of L-NMMA was also assessed during infusion of sodium nitroprusside (0.8, 1.6, and 3.2 microg/min), an exogenous NO donor. Drugs were infused into the brachial artery, and forearm blood flow was measured by plethysmography. The vasodilator effect of isoproterenol was significantly blunted during the administration of L-NMMA compared with saline (maximum flow, 7.7 +/- 4 versus 11.2 +/- 5 mL x min(-1) x dL(-1), respectively; P<.001). In contrast, the vasodilator response to sodium nitroprusside was not significantly affected by the infusion of L-NMMA (maximum flow, 8.8 +/- 3.7 mL x min(-1) x dL(-1) during L-NMMA versus 8.9 +/- 3.2 mL x min(-1) x dL(-1) during saline; P=.25). These findings indicate that NO inhibition blunts the vasodilator effect of beta-adrenergic agonists in the human forearm and suggest that an abnormal response to adrenergic stimulation may occur in conditions associated with impaired NO activity.

Adrenergic beta-Agonists↗

PubMed1996

Relation of stress testing and ambulatory blood pressure to hypertensive cardiac damage.

In essential hypertension, the severity of cardiovascular damage is only weakly related to clinic blood pressure (BP), whereas a better relationship seems to exist with BP recorded during stressful situations. The present study compared BP levels measured during laboratory stress testing and 24-h ambulatory monitoring with regard to their relationship with cardiac end-organ involvement. BP recorded during a mental and a physical challenge and during 24-h ambulatory monitoring was related to Doppler echocardiography characteristics of left ventricular structure and filling in 63 untreated essential hypertensives and in 32 healthy subjects. In the hypertensive group, only a weak relationship was observed between left ventricular mass and clinic BP; the strength of this association was not improved by BP measured during mental task and cycle ergometry, and was slightly but not significantly higher for BP recorded during ambulatory monitoring. In multivariate analysis, left ventricular mass was independently predicted by stroke index and 24-h systolic BP. Among the different pressure measures, 24-h, daytime, and nighttime BPs bore the only significant relation to relative wall thickness. In the normotensive group, no significant relationship was observed between left ventricular mass and different measures of BP. Doppler indexes of left ventricular diastolic filling did not significantly relate to any BP measurement in the hypertensive group, and generally bore a significant inverse relationship to various BP recordings in the normotensive group. To summarize, stress testing BP does not help in identifying hypertensive patients with increased left ventricular mass.

Adult↗

PubMed1995

Evidence that endothelial dysfunction in patients with hypercholesterolemia is not due to increased extracellular nitric oxide breakdown by superoxide anions.

Patients with hypercholesterolemia have impaired endothelium-dependent vasodilation due to decreased nitric oxide activity. The present study aimed to determine whether this form of endothelial dysfunction is related to enhanced extracellular breakdown of nitric oxide by superoxide anions. To this end, the vascular responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct smooth muscle dilator) were studied before and after combined administration of copper-zinc superoxide dismutase (a scavenger of superoxide anions with poor intracellular penetrance; 6,000 U/min) in 20 normal controls (11 men and 9 women, age 50 +/- 6 years) and in 20 hypercholesterolemic patients (10 men and 10 women, age 49 +/- 9 years). Drugs were infused into the brachial artery and the response of the forearm vasculature was measured by plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypercholesterolemic patients compared with normal controls (maximal flow 8.8 +/- 2 vs 12.7 +/- 3 ml/min/100 ml, respectively; p < 0.03); however, no difference was observed in the response to sodium nitroprusside (9.7 +/- 2 and 9.5 +/- 3 ml/min/100 ml). In normal controls, the infusion of superoxide dismutase did not significantly modify the response to acetylcholine (maximal flow 12.7 +/- 3 vs 12.1 +/- 3 ml/min/100 ml before and after superoxide dismutase, respectively). Similarly, in hypercholesterolemic patients, the infusion of superoxide dismutase did not alter the response to acetylcholine (maximal flow 8.8 +/- 2 and 8.9 +/- 2 ml/min/100 ml). A subset of 19 subjects (8 normal and 11 patients) received a 60-minute infusion of superoxide dismutase at 24,000 U/min without alteration in their response to acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1995

Effect of copper-zinc superoxide dismutase on endothelium-dependent vasodilation in patients with essential hypertension.

Patients with essential hypertension have abnormal endothelium-dependent vasodilation related to decreased nitric oxide activity. The specific mechanism responsible for this abnormality is unknown. Recent studies in hypertensive animals have suggested an augmented destruction of nitric oxide by superoxide anions. Therefore, in the present study we aimed to investigate whether this mechanism is responsible for the abnormal vasodilator function of hypertensive patients. To this end, we studied the vascular responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct smooth muscle dilator) before and after combined administration of copper-zinc superoxide dismutase (a scavenger of superoxide anions with poor intracellular penetrance; 6000 U/min) in 20 healthy control subjects (11 men and 9 women; aged 50 +/- 6 years) and 20 hypertensive patients (13 men and 7 women; aged 51 +/- 9 years). Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypertensive patients compared with control subjects (maximal flow: 8.2 +/- 4 versus 12.7 +/- 3 mL/min per 100 mL; P < .02); however, no difference was observed in the response to sodium nitroprusside (8.1 +/- 4 versus 9.5 +/- 3 mL/min per 100 mL). In healthy control subjects superoxide dismutase infusion did not modify the vasodilator response to acetylcholine (maximal flow: 12.7 +/- 3 before versus 12.1 +/- 3 after superoxide dismutase). Similarly, in hypertensive patients superoxide dismutase infusion did not alter the response to acetylcholine (maximal flow: 8.2 +/- 4 versus 7.7 +/- 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1994

Effects of benazepril on stress testing blood pressure in essential hypertension.

The effects of different doses of the angiotensin-converting enzyme inhibitor benazepril on cardiovascular response to a set of standardized laboratory tasks were analyzed. Eighteen patients (15 men and 3 women) with mild-to-moderate essential hypertension were randomly allocated to receive 10 or 20 mg of benazepril, or placebo, each administered once daily for 2 weeks, according to a double-blind, 3-period design. At the end of each treatment period, patients were examined at resting baseline and while performing mental arithmetic, handgrip and cycle ergometry tests. In comparison with placebo, the average reductions in resting systolic blood pressure (BP) were 8.7 mm Hg (95% confidence intervals [CI] -15.2 to -2.1) with 10 mg of benazepril, and 7.8 mm Hg (95% CI -14.4 to -1.3) with 20 mg; the corresponding reductions in resting diastolic BP were 5.1 mm Hg (95% CI -8.7 to -1.4) and 6.8 mm Hg (95% CI -10.4 to -3.1) (all p < 0.05). During mental arithmetic, the reductions in systolic BP were 10.4 mm Hg (95% CI -17.4 to -3.4) with 10 mg of benazepril, and 13.8 mm Hg (95% CI -20.8 to -6.8) with 20 mg; diastolic BP was reduced by 4.5 mm Hg (95% CI -8.5 to -0.5) and 8.3 mm Hg (95% CI -13.2 to -4.3), respectively (all p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗