ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Our objectives were to (1) test the hypothesis that nitric oxide (NO) contributes to peak reactive hyperemia (RH) in the human peripheral vasculature, (2) examine the impact of atherosclerosis and its risk factors on RH, and (3) investigate whether L-arginine will improve RH in patients with endothelial dysfunction. The endothelium contributes to shear stress-mediated vasomotion by releasing a variety of dilating factors, including NO, but the contribution of NO to peak RH in patients with and without endothelial dysfunction is unknown. Endothelium-dependent and endothelium-independent function was assessed with intrafemoral arterial acetylcholine (ACh) and sodium nitroprusside. RH was produced by occlusion of blood flow to the leg for 3 minutes. The study was repeated after NG-monomethyl-L-arginine(L-NMMA) in 44 subjects and L-arginine in 9 patients with atherosclerosis. There were 15 normal control subjects without risk factors for atherosclerosis and 29 patients with risk factors or angiographic atherosclerosis. Microvascular vasodilation in response to ACh, but not to sodium nitroprusside, was lower in the patients with risk factors or atherosclerosis compared with normal control subjects, P=0.048, and the inhibition of ACh-induced microvascular dilation by L-NMMA was also greater in normal control subjects (P=0.045). Similarly, RH, including the peak response, was inhibited by L-NMMA in normal control subjects (P=0.0011) but not in patients with risk factors or atherosclerosis, suggesting that the contribution of NO to both ACh-induced dilation and RH was diminished in patients with risk factors or atherosclerosis. L-Arginine did not affect vasodilation in response to ACh, sodium nitroprusside, or RH. We concluded that (1) NO contributes to all phases of RH in the normal human peripheral vasculature, (2) patients with atherosclerosis or its risks have abnormal NO bioactivity in response to pharmacological and physiological stimulation, and (3) L-arginine does not improve RH in atherosclerosis. Reduced physiological vasodilation in atherosclerosis may contribute to or exacerbate hypertension and ischemia. (Hypertension. 1998;32:9-15.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Endothelial function has been shown to be impaired in patients with essential hypertension. The purpose of the present study was to determine whether antihypertensive drug therapy improves impaired endothelium-dependent renal vasorelaxation in essential hypertensive patients without atherosclerosis. We evaluated the effects of intravenous infusion of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 27 patients with mild to moderate essential hypertension who were randomly assigned to treatment with either the angiotensin-converting enzyme inhibitor imidapril or the calcium antagonist amlodipine for 12 weeks in a double-blind fashion. After the 12 weeks, the decrease in blood pressure was similar in the imidapril (n=14) and amlodipine (n=13) groups. The increase in renal plasma flow was also similar in both groups. L-Arginine-induced renovascular relaxation was increased by imidapril (renal plasma flow, 9.6 +/- 5.1% to 14.4 +/- 7.4%; renal vascular resistance, -10.4 +/- 8.1% to -16.7 +/- 9.2%, P<0.05, respectively) but not by amlodipine. Urinary excretion of nitrite/nitrate in response to L-arginine was significantly increased by imidapril (90 +/- 29% to 134 +/- 63%, P<0.05) but remained unchanged by amlodipine. These findings suggest that angiotensin-converting enzyme inhibition improves the impaired endothelium-dependent renovascular relaxation in patients with essential hypertension due to the increase in nitric oxide production and that the reduction in blood pressure with a calcium antagonist does not play a major role in the potentiation of L-arginine/nitric oxide-mediated effects. (Hypertension. 1998;32:16-24.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Intimal-medial thickening of the carotid wall is considered an early marker of atherosclerosis. Endothelial function is impaired in the presence of various cardiovascular risk factors that are implicated in the pathogenesis of atherosclerosis. To evaluate the relationship between vascular reactivity and carotid intimal-medial thickening, in 44 (mean +/- SD age, 45.7 +/- 8.8 years; range, 28 to 60 years; 31 men and 13 women) patients with essential hypertension who had never been treated and whose history of increased blood pressure was no longer than 12 months, we evaluated several parameters: intimal-medial thickening of the common carotid arteries (by B-mode ultrasound); forearm vascular response (by strain-gauge plethysmography) to intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 [micro sign]g/100 mL forearm tissue per minute), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, and 4 [micro sign]g/100 mL forearm tissue per minute), an endothelium-independent vasodilator; calculated minimal forearm vascular resistances (the ratio between mean arterial pressure and maximal forearm vasodilation induced by 13 minutes of ischemia and 1 minute of exercise); and left ventricular mass index (on echocardiography profile). Carotid wall intimal-medial thickening showed a significant (P<0.001) inverse correlation with vasodilation to acetylcholine (r=-0.58) and age (r=-0.40), whereas no correlation was observed with the response to sodium nitroprusside or with minimal forearm vascular resistances, left ventricular mass index, systolic and diastolic blood pressures, and plasma cholesterol and glucose levels. Moreover, vasodilation to acetylcholine showed no correlation with minimal forearm vascular resistances or left ventricular mass index. Although comparison of different vascular "districts," such as the forearm microcirculation and carotid artery, does not allow for a conclusive interpretation, the present data indicate that in patients with essential hypertension, carotid wall thickening is associated with reduced endothelium-dependent vasodilation and suggest that endothelial dysfunction might be involved in early arterial structural alterations.(Hypertension. 1998;32:25-32.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Previous studies have reported evidence of an important interaction between nitric oxide (NO) and prostaglandins in the acute regulation of renal function. The objective of this study was to determine in conscious dogs whether the renal effects of the prolonged administration of a cyclooxygenase inhibitor are enhanced when NO synthesis is reduced. Meclofenamate infusion (5 [micro sign]g [middle dot] kg-1[middle dot] min-1) during 4 consecutive days (n=8) elicited a continuous decrease (P<0.05) in renal blood flow and plasma renin activity and a transitory decrease in sodium excretion. NG-Nitro-L-argininemethyl ester (L-NAME) infusion (5 [micro sign]g [middle dot] kg-1[middle dot] min-1) during 6 days (n=8) produced a significant increase in arterial pressure and a transitory decrease (P<0.05) in both renal blood flow and plasma renin activity. The simultaneous inhibition of NO and prostaglandin synthesis (n=7) led to an increase in arterial pressure and a decrease in renal blood flow similar to those observed during the administration of either L-NAME or meclofenamate. In contrast, this simultaneous inhibition produced a decrease in glomerular filtration rate, which was not observed in the previous groups, and also induced an increase in renal vascular resistance and a decrease in sodium excretion greater (P<0.05) than those found during the inhibition of either NO or prostaglandins. Only a transitory decrease in plasma renin activity was found during meclofenamate infusion in this group. The results of this study present new evidence that the renal vasoconstrictor and antinatriuretic effects induced by the prolonged infusion of a cyclooxygenase inhibitor are significantly enhanced when NO synthesis is reduced. These results suggest that renal function may be more sensitive to the prolonged administration of a cyclooxygenase inhibitor in situations where NO production is reduced.(Hypertension. 1998;32:33-38.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The cardiovascular effect of estrogen is currently under intense investigation, but the role of androgens in vascular biology has attracted little attention. Because endothelial repair and vascular smooth muscle cell (VSMC) proliferation affect atherogenesis, we analyzed the effects of 17 beta-estradiol (E2), dihydrotestosterone (DHT), and sex hormone antagonists on DNA synthesis in human umbilical VSMCs and in E304 cells (a human umbilical endothelial cell line). In VSMCs, both E2and DHT had a biphasic effect on [(3) H]thymidine incorporation into DNA: low concentrations (0.3 nmol/L for E2, 3 nmol/L for DHT) stimulated [(3) H]thymidine incorporation (+35% and +41%, respectively), whereas high concentrations (30 nmol/L for E2, 300 nmol/L for DHT) inhibited [(3) H]thymidine incorporation (-40%). In contrast, E2(0.3 to 300 nmol/L) and DHT (3 to 3000 nmol/L) dose-dependently enhanced [(3) H]thymidine incorporation in E304 cells (peak, +85% for both). In VSMCs, high concentrations of E2and DHT inhibited platelet-derived growth factor (PDGF)-or insulin-like growth factor (IGF-1)-induced DNA synthesis (-50% to 80%), whereas PDGF- or IGF-1-dependent DNA synthesis in E304 cells was further increased by E2. The antiestrogens tamoxifen and raloxifene mimicked the effects of E2on DNA synthesis in both VSMCs and E304 cells. However, when coincubated with a stimulatory concentration of E2(0.3 nmol/L), tamoxifen and raloxifene blocked E2-induced[(3) H]thymidine incorporation in E304 cells but not in VSMCs. Finally, the androgen antagonist flutamide inhibited the biphasic effects of DHT on VSMCs and blocked the increase in DNA elicited by DHT in E304 cells. The results suggest complex, dose-dependent, and cell-specific interactions of estrogens, androgens, and their respective antagonists in the control of cellular proliferation in the vascular wall. Gonadal steroid-dependent inhibition of VSMC proliferation and stimulation of endothelial replication may contribute to vascular protection and remodeling responses to vascular injury. (Hypertension. 1998;32:39-45.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Several lines of evidence suggest that peripheral osmoreceptors respond to alterations in dietary NaCl by adjusting renal sympathetic nerve activity, but the impact of this reflex on the long-term regulation of mean arterial pressure (MAP) remains unclear. The present study tested the hypothesis that denervation of peripheral osmoreceptors elevates arterial pressure and induces NaCl-sensitive hypertension in normotensive rats. Hepatic denervated and sham-operated Wistar-Kyoto rats were instrumented with telemetry probes for continuous monitoring of MAP and heart rate. After 1 week on a basal (0.6%) NaCl diet, the rats were fed a high (8%) NaCl diet for 2 weeks. On the basal NaCl diet, MAP in hepatic denervated rats was 15 +/- 1 mm Hg higher than in sham-operated rats. The high NaCl diet did not significantly increase MAP above baseline levels in either denervated or sham-operated rats, but the amplitude of the 24-hour rhythm of arterial pressure increased significantly more in the denervated than in the sham-operated rats. In a second experiment, two similar groups of rats were fed a very low (0.05%) NaCl diet. Mean arterial pressure of the denervated group was significantly higher than that of the sham-operated rats on either the basal or the very low NaCl diet, but the very low NaCl diet did not affect arterial pressure in either group. These results suggest that in the rat, although hepatic osmoreceptors contribute to long-term arterial pressure regulation, they contribute much less to dietary NaCl-induced changes in arterial pressure. (Hypertension. 1998;32:46-51.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

0.15 Hz obtained by the Portapres was similar during the day but lower during the night when compared with those obtained by intra-arterial recordings (P<0.01). No differences were observed between Portapres and intra-arterial recordings for any estimation of pulse interval variabilities. The overestimation of BP variability by Portapres remained constant over virtually the entire 24-hour recording period. Thus, although clinical studies are still needed to demonstrate the clinical relevance of finger BP variability, our study shows that Portapres can be used with little error to estimate 24-hour BP variabilities if diastolic and mean BPs are used. For systolic BP, the greater error can be minimized by using correction factors. (Hypertension. 1998;32:52-58.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Superoxide radical (O2-) is increased in the vessel wall of spontaneously hypertensive rats (SHR) where its blockade potentiates endothelium-dependent vasodilation. The purpose of this study was to determine the role of O2-in the hypertension and renal vasoconstriction of SHR and its interaction with nitric oxide (NO). Baseline mean arterial pressure (MAP) and renal vascular resistance were markedly elevated in SHR (n=6) compared with Wistar-Kyoto rats (WKY; n=6) (145 +/- 4 versus 118 +/- 4 mm Hg, P<0.05, and 24 +/- 3 versus 17 +/- 1 mm Hg [middle dot] mL-1[middle dot] min-1, respectively; P<0.05). The stable membrane-permeable superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl (tempol; 72 [micro sign]mol/kg IV) normalized MAP (103 +/- 9 versus 96 +/- 6 mm Hg for SHR and WKY, respectively) and RVR (17 +/- 2 versus 15 +/- 1 mm Hg [middle dot] mL-1[middle dot] min-1) of SHR. The MAP of SHR was more sensitive and responsive to graded infusions of tempol (0, 1.8, 18, 180, and 1800 [micro sign]mol [middle dot] kg-1[middle dot] h-1IV) than that of WKY. To determine whether O (2)-increases MAP by inactivation of NO, its synthesis was blocked in SHR with Nw-nitro-L-argininemethyl ester (L-NAME, 11 [micro sign]mol [middle dot] kg-1[middle dot] min-1IV, n=6). Whereas tempol alone significantly reduced MAP by 32% (184 +/- 12 to 121 +/- 18 mm Hg, P<0.05, n=6), L-NAME infusion abolished the MAP response to tempol (187 +/- 8 to 186 +/- 4 mm Hg, n=5). In contrast, tempol did reduce MAP of SHR (188 +/- 7 to 161 +/- 7 mm Hg, P<0.05) where MAP was elevated by norepinephrine (31 nmol [middle dot] kg-1[middle dot] min-1IV, n=6). Finally, to determine the longer-term effect of O2-, tempol (1.5 mmol [middle dot] kg-1[middle dot] d-1IP) was given for 7 days. Tempol had no effect on MAP in WKY (96 +/- 1 to 97 +/- 1 mm Hg, n=7) but significantly decreased MAP in SHR (133 +/- 2 to 120 +/- 3 mm Hg, P<0.05, n=7). These data implicate O2-in the hypertension of SHR in vivo. The antihypertensive action of tempol depends on NO synthesis presumably because O2-inactivates NO and thus diminishes its vasodilatory actions. (Hypertension. 1998;32:59-64.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID