ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin (AM), which are both derived from proadrenomedullin, exhibit marked hypotensive effects. We recently reported that PAMP but not AM reduced the release of norepinephrine from peripheral sympathetic nerve endings. Our present objective was to clarify the involvement of the sympathetic nervous system in the hypotensive action of PAMP and AM. Intravenous administration of PAMP (10, 20, and 50 nmol/kg) to conscious rats induced less reflex tachycardia (5 plus/minus 5, 10 plus/minus 5, and 14 plus/minus 6 beats per minute [bpm]) than that of AM in 0.1, 0.5, and 1.0 nmol/kg doses (5 plus/minus 8, 20 plus/minus 7, and 38 plus/minus 5 bpm, P < .01) although both agents showed similar hypotensive effects. We evaluated the effect of PAMP on blood pressure in pithed rats whose sympathetic nervous systems were abolished. In pithed rats, AM (-2 plus/minus 1, -7 plus/minus 1, and -10 plus/minus 3 mm Hg; NS, P < .05, and P < .01, respectively) but not PAMP evoked hypotension. In contrast, administration of PAMP (-3 plus/minus 1, -11 plus/minus 2, and -14 plus/minus 4 mm Hg; P < .05, P < .01, and P < .01, respectively) as well as adrenomedullin (-2 plus/minus 2, -10 + 3, and -15 plus/minus 4 mm Hg; NS, P < .01, and P < .01) significantly reduced blood pressure in electrically stimulated, pithed rats, which had reached almost the same levels as in conscious rats. In electrically stimulated, pithed rats, plasma norepinephrine level was reduced by PAMP but not by vehicle or AM. These findings suggest that the hypotensive effect of PAMP is mainly due to inhibition of peripheral sympathetic nerve activity. (Hypertension. 1996;28:325-329.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

.05.). Vasodilator responses to the endothelium-independent agent sodium nitroprusside (1.6 micro gram/min) were also unchanged after estrogen supplementation. However, estrogen enhanced vasoconstrictor responses to the nitric oxide synthase inhibitor NG-monomethyl-L-arginine at doses of 1, 2, and 4 micro mol/min (fall in forearm blood flow before estrogen: 13 plus/minus 9%, 20 plus/minus 7%, and 26 plus/minus 8%, respectively; after estrogen: 18 plus/minus 9%, 36 plus/minus 7%, and 47 plus/minus 7%, P = .04). Responses to vasoactive agents were unchanged after administration of placebo. Thus, in perimenopausal women, estrogen supplementation reduces blood pressure and enhances basal but not acetylcholine-induced nitric oxide release in forearm resistance arteries. (Hypertension. 1996;28:330-334.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In response to a high salt intake, salt-sensitive hypertensive individuals retain more sodium and manifest a rise in blood pressure greater than that in salt-resistant individuals. In this study, we tested whether salt sensitivity might be related at least in part to reduced secretion of atrial natriuretic peptide (ANP) or to abnormal nitric oxide production. We measured plasma ANP and NO2+ NO3in 7 normotensive individuals and 13 salt-sensitive and 14 salt-resistant blacks with essential hypertension under conditions of low (10 mEq/d) and high (250 mEq/d) salt intake. To evaluate possible racial differences in ANP secretion, we also measured plasma ANP in 6 salt-sensitive and 8 salt-resistant hypertensive whites during low and high salt intakes. Under low salt conditions, plasma ANP levels were not different in normotensive control subjects and salt-sensitive and salt-resistant hypertensive blacks. During high salt intake, plasma ANP levels did not change in control subjects and salt-resistant patients but decreased in salt-sensitive patients. ANP levels after high salt diet were lower (P < .01) in salt-sensitive than salt-resistant blacks. In hypertensive whites, high salt intake caused no significant change in plasma ANP. Under low salt conditions, plasma NO2+ NO3levels were higher (P < .05) in salt-sensitive (189 plus/minus 7.9 micro mol/L) and salt-resistant (195 plus/minus 13.5 micro mol/L) black patients than in control subjects (108 plus/minus 9.7 micro mol/L). During high salt intake, plasma NO2+ NO3decreased significantly (P < .01) in both salt-sensitive (150 plus/minus 7.0 micro mol/L) and salt-resistant (142 plus/minus 9.0 micro mol/L) patients. These studies show that under conditions of high salt intake, salt-sensitive hypertensive blacks manifest a paradoxical decrease in ANP secretion. This abnormality may play a role in the reduced ability of these individuals to excrete a sodium load and in the sodium-induced rise in blood pressure. This study does not support the hypothesis that salt sensitivity depends on a deficit of nitric oxide production, but it suggests that high salt intake may alter the endothelium-dependent adaptation of peripheral resistance vessels. (Hypertension. 1996;28:335-340.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Intravenous injection of NG-nitro-L-arginine (L-NA), a nitric oxide synthase inhibitor, elevated mean blood pressure by 29.0 plus/minus 4.9 mm Hg and decreased heart rate by 40.7 plus/minus 5.6 beats per minute in anesthetized Japanese monkeys (n = 6), whereas N (G) -nitro-D-arginine was without effect. After pretreatment with pentolinium, the magnitude of the pressure elevation by L-NA was significantly less than that after pretreatment with phentolamine. The reduced blood pressure by either of the pretreatment drugs was compensated to control levels by a continuous infusion of angiotensin II before L-NA administration. Isolated monkey distal mesenteric arteries (150 to 200 micro meter OD) without endothelium responded to nerve stimulation by nicotine with a contraction, which was abolished by prazosin alone or in combination with alpha, beta-methylene ATP. In the strips thus treated and contracted with prostaglandin F2alpha, nicotine caused a relaxation that L-NA abolished. L-NA but not NG-nitro-D-arginine reversed the inhibition. Histochemical staining of NADPH diaphorase, considered to be identical to nitric oxide synthase in neuronal tissues, demonstrated that positively stained nerve fibers were consistently present in the adventitia of monkey distal mesenteric arteries and arterioles. These results strongly suggest that nitroxidergic vasodilator nerves innervate peripheral small arteries and arterioles in the monkey and that these nerves participate in the regulation of systemic blood pressure. High blood pressure caused by nitric oxide synthase inhibitors is associated with an elimination of nitroxidergic nerve function together with an impairment of the basal release of nitric oxide from the endothelium. (Hypertension. 1996;28:341-346.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In this study, we examined whether air-jet stress-induced active sympathetic hindlimb vasodilation in conscious rats involves the release of preformed stores of nitric oxide-containing factors. We determined the effects of repeated episodes of air-jet stress (six episodes given 5 minutes apart) on mean arterial pressure and vascular resistances in the mesenteric bed and intact and sympathetically denervated hindlimb beds of conscious rats treated with saline or the nitric oxide synthesis inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 25 micro mol/kg IV). In saline-treated rats, air-jet stress produced alerting behavior, minor changes in blood pressure, pronounced mesenteric vasoconstriction, and immediate and marked vasodilation in the sympathetically intact hindlimb but a minor vasodilation in the sympathetically denervated hindlimb. Each air-jet stress produced virtually identical responses. In L-NAME-treated rats, the first air-jet stress produced vasodilator responses in the sympathetically intact and sympathetically denervated hindlimbs that were similar to those in the saline-treated rats. However, each subsequent air-jet stress produced progressively smaller vasodilator responses in the sympathetically intact but not the sympathetically denervated hindlimb. There was no loss of air-jet stress-induced alerting behavior or mesenteric vasoconstriction, suggesting that L-NAME did not interfere with the central processing of the air-jet or the resultant changes in autonomic nerve activity. The progressive diminution of air-jet stress-induced vasodilation in the intact hindlimb of L-NAME-treated rats may be due to the use-dependent depletion of preformed stores of nitric oxide-containing factors that cannot be replenished in the absence of nitric oxide synthesis. (Hypertension. 1996;28:347-353.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In the present study, we examined the possibility that the endothelium-dependent vasodilators acetylcholine and bradykinin release preformed pools of nitric oxide-containing factors. Successive injections of selected doses of acetylcholine (1.18 plus/minus 0.3 micro gram/kg IV) or bradykinin (5 micro gram/kg IV) caused reproducible hypotensive and vasodilator responses within sympathetically intact and sympathetically denervated hindlimbs of conscious rats. After administration of the nitric oxide synthesis inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 25 micro mol/kg IV), the first injection of acetylcholine or bradykinin produced pronounced depressor and vasodilator responses that, in the case of bradykinin, were greater than those observed before L-NAME administration. However, each successive injection of acetylcholine and bradykinin produced progressively smaller responses, such that the later injections elicited a markedly diminished hypotension and vasodilation. This "use-dependent" loss of endothelium-dependent vasodilation was not due to the diminished vasorelaxant potency of nitric oxide-containing factors because the vasodilator effects of the nitric oxide donor sodium nitroprusside (32 micro gram/kg IV) and the S-nitrosothiol compound S-nitro-socysteine (200 nmol/kg IV) were augmented in the presence of L-NAME. These results suggest that the use-dependent loss of the hemodynamic effects of acetylcholine and bradykinin in L-NAME-treated rats may be due to the release and subsequent depletion of a factor whose synthesis depends on the bioavailability of nitric oxide. Taken together, these results suggest that preformed pools of nitric oxide-containing factors exist within the endothelium of resistance vessels and that endothelium-dependent agonists exert their vasorelaxant effects at least in part by the mobilization of these preformed pools. (Hypertension. 1996;28:354-360.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Chronic administration of NG-nitro-L-arginine methyl ester (L-NAME) induces a rise in blood pressure that is prevented by angiotensin I-converting enzyme inhibitors or angiotensin II receptor (type 1) blockade. Alterations in vascular reactivity in this model have not been extensively studied and could potentially be involved in the pathogenesis of L-NAME-induced hypertension. In the present work, we aimed to study the vascular reactivity and cGMP content of aortic ring segments isolated from Wistar rats treated for 3 weeks with L-NAME or L-NAME plus the converting enzyme inhibitor quinapril. Quinapril prevented the rise in blood pressure in L-NAME-treated rats although acetylcholine-induced dilation in aortic rings was suppressed and sodium nitroprusside-induced dilation was increased in both L-NAME- and L-NAME plus quinapril-treated rats. In isolated aortic ring segments, chronic L-NAME decreased the contractile response to Potassium+(125 mmol/L), phenylephrine, angiotensin II, the G protein stimulator AlF4-, and the protein kinase C activator phorbol dibutyrate. In contrast to the upregulated sodium nitroprusside-induced dilation, the contractile capacity of the aorta in response to angiotensin II, phenylephrine, AlF4-, Potassium+, and phorbol dibutyrate was restored by quinapril. Aortic cGMP was lowered in rats treated with L-NAME (530 plus/minus 120 fmol/mg protein, n = 12, P < .05) and L-NAME plus quinapril (461 plus/minus 140 fmol/mg protein, n = 12, P < .05) compared with controls (1798 plus/minus 522 fmol/mg protein, n = 12). We hypothesize that the continuous nitric oxide blockade by L-NAME might attenuate a continuous endogenous relaxing tone and is associated with an upregulated endogenous vasoconstrictor tone in large arteries. Converting enzyme inhibition interfered more with the increased endogenous constrictor tone than with the decreased vasodilator tone in the wall of large arteries from L-NAME-treated rats. (Hypertension. 1996;28:361-366.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We examined the role of nitric oxide (NO) in the inherited resistance or susceptibility to hypertension in the Sabra hypertension-prone (SBH) and hypertension-resistant (SBN) rat. Basal mean arterial blood pressure was significantly greater in SBH than in SBN rats. Phenylephrine elevated blood pressure to a similar extent in both substrains, whereas the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) had a greater pressor effect in SBN rats. The vasoconstrictor potency of phenylephrine was significantly higher in endothelium-intact aortic rings from the SBH rat, whereas the vasoconstrictor potency of L-NMMA was higher in those from the SBN substrain. Acetylcholine-induced endothelium-dependent relaxation was greater in aortic rings from SBN rats. The vasodilator potency of glyceryl trinitrate was significantly higher in aortic rings from SBH rats and was enhanced after endothelium removal. Both the activity of calcium-dependent NO synthase from aortic endothelial cells and the basal concentration of nitrite/nitrate in plasma were significantly greater in SBN than in SBH rats. In normotensive Wistar rats, basal mean arterial blood pressure, the pressor effect of L-NMMA, endothelial NO synthase activity, and plasma nitrite/nitrate concentrations were all between the values in SBH and SBN rats. These results indicate that a decrease in NO generation plays a role in the susceptibility of SBH rats to hypertension. Furthermore, the resistance to hypertension in the SBN strain may be related to increased NO generation. (Hypertension. 1996;28:367-371.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

It is known that endothelin-1 stimulates the release of nitric oxide and prostaglandins in various vascular beds. We designed the present study to analyze the roles of prostaglandins and nitric oxide in the effect of endothelin-1 on the regulation of renal hemodynamics and renin release. We used Nomega-nitro-L-arginine methyl ester (L-NAME) and meclofenamic acid to inhibit the production of nitric oxide and prostaglandins, respectively. With a nonfiltering kidney model, renal blood flow was reduced 21% in dogs treated with L-NAME and 18% in dogs treated with meclofenamic acid. Inhibition of nitric oxide and prostaglandins, however, produced opposite effects on estimated glomerular hydraulic pressure: L-NAME increased glomerular hydraulic pressure from 63.1 plus/minus 0.9 to 64.6 plus/minus 1.3 mm Hg (P < .01), and meclofenamic acid reduced glomerular hydraulic pressure from 63.3 plus/minus 1.4 to 59.8 plus/minus 1.6 mm Hg (P < .01). Endothelin-1 infusion produced a dose-dependent reduction in renal blood flow after blockade of nitric oxide and prostaglandins. The responses of glomerular hydraulic pressure were different in the two groups during endothelin-1 infusion. Endothelin-1 progressively reduced glomerular hydraulic pressure in a dose-dependent fashion in the meclofenamic acid group. However, endothelin-1 slightly increased glomerular hydraulic pressure until the infusion rate reached 5.0 ng/kg per minute. At that rate, endothelin-1 reduced glomerular hydraulic pressure from 63.3 plus/minus 1.4 to 47.0 plus/minus 1.4 mm Hg in the meclofenamic acid group (P < .01), a more than 25% reduction, whereas at the same dose, endothelin-1 reduced glomerular hydraulic pressure only less than 2% in the L-NAME group. In addition, blockade of nitric oxide and prostaglandins did not alter the inhibitory effect of endothelin-1 on renin release in the nonfiltering kidney. Therefore, the present study demonstrates that the release of nitric oxide and prostaglandins might modulate the effects of endothelin-1 on the renal circulation. The present findings suggest that the differential vasoconstrictive effects of endothelin-1 on preglomerular and postglomerular vessels are associated with its stimulation of nitric oxide and prostaglandin production. (Hypertension. 1996;28:372-378.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID