摘要:

Previously we reported that immunoreactive angiotensin II (Ang II) release from isolated perfused rat mesenteric arteries was mediated by β-adrenergic receptor activation. However, the precise mechanism of regulation of vascular renin-angiotensin is not completely understood. In this study, we examined the effect of indomethacin and medofenamate on immunoreactive angiotensin I (Ang I) and Immunoreactive Ang II release from perfused rat hind leg vasculature to delineate the possible relevance of prostaglandins to the vascular renin-angiotensin system in vitro. We also examined the effects of isoproterenol and propranolol on the immunoreactive Ang I and II release. Isolated rat hind legs were perfused with Krebs-Ringer solution, and immunoreactive Ang I and II released into the perfusate were measured directly by using a Sep-Pak CSs18cartridge connected to the perfusion system. Indomethacin and meclofenamate (10−8to 2 × 10−6M) added to the perfusion medium suppressed immunoreactive Ang I and II release to similar extents in a dose-dependent manner (p< 0.001); the maximal percent inhibition of immunoreactive Ang II release evoked by these Inhibitors (2 × 10−6M) was 60 ± 6% {p< 0.001) for indomethacin and 50 ± 4% (p< 0.001) for meclofenamate. Isoproterenol (10−6M) failed to cause a change in the release of both pep tides, but propranolol (10−6M) slightly decreased the release of immunoreactive Ang I and II by 28 ± 4% (p< 0.001) and 32 ± 4% (p< 0.001), respectively. There was a highly significant positive correlation between the released amount of immunoreactive Ang I and that of immunoreactive Ang II altered by indomethacin (r= 0.91), meclofenamate (r= 0.94), or propranolol administration (r= 0.90). These results suggest that the renin-angiotensin in the hind legs is modulated by prostaglandins and that a difference exists in the β-adrenergk receptor-mediated release of Ang II among diverse vascular beds.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Chronic microcirculatory alterations produced by prolonged use of a vasoactive drug were repeatedly observed in the same skeletal muscle vessels of the dorsal microcirculatory chamber. Arterioles and venules with diameters averaging from 70 to 90 /tm, the size range contributing most to peripheral vascular resistance, were measured daily for 6 days to determine differences in diameter, tortuosity, and number of branches. Hydralazine was given as a subcutaneous pellet (2.5 mg), with a release life of 21 days. Hydralazine caused a 39% dilation in arterioles of Wistar-Kyoto rats (WKY) at 3 hours but only an 8% dilation in those of spontaneously hypertensive rats (SHR). At 6 hours, arterioles In both groups were similarly dilated (30–33%). Beyond 6 hours, both SHR and WKY arterioles returned to their prehydralazine control diameter, even though arterial pressure was still reduced. By Day 6, in WKY, but not SHR, there was an increase in the tortuosity of arterioles and a tendency for an hicrease in their number. Venous diameter was also increased on Day 6, consistent with the fluid retention effect of hydralazine. These data indicate that some so-called vasodilators may cause long-term alterations in growth of vessels rather than an increase in vessel caliber.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Renal sympathetic antidiuretic, antinatriuretic, and vasoconstrictor responses are mediated by a,-adrenergic receptors in the normal rat. Since the renal nerve has been implicated in the pathogenesis of rat genetic hypertension, we investigated renal <x,-adrenergic receptor coupling to phosphoinositide turnover in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In cortical slices from adult (13-week-oM) SHR and WKY, stimulation with norepinephrine (l0 M 0−3M) caused a concentrationdependent increase in accumulation of [3H]inositol phosphates. However, dose-response curves for SHR characteristically displayed a depression of the maximum response as compared with those for WKY. Baseline accumulation of [3H]inositol phosphates was not different between strains (39.4 ± 2.2 cpm/mg tissue/hr for WKY and 34.4 ± 2.1 cpm/mg tissue/hr for SHR slices;n= 5 rats/group, determined in triplicate). Antagonist competition studies revealed that norepinephrine-stimulated (10∼4M) [3H] inositol phosphate accumulation was mediated by a,-adrenergic receptors (ICj,) for prazosin: 65 ± 11 nM for SHR and 64 ± 5 nM for WKY). The reduction in norepinephrine-stimulated [3H]inositol phosphate accumulation in SHR cortex was not the result of the hypertension, since it was also present in cortical slkes from young (4-week-old) SHR in which the blood pressure was not yet significantly different from that in WKY and since [3H]inositol phosphate accumulation was unchanged from control values in rats made hypertensive by treatment with deoxycorticosterone acetate. Scatchard analysis of [3H]prazosin binding in renal cortical membranes of young and adult SHR and WKY revealed no significant differences in aradrenergk receptor density or affinity between strains at either age. Our results suggest that renal o,-adrenergic receptor coupling to phospholipase C is less efficient in SHR than in WKY. This unpaired response is not the result of hypertension or changes in receptor density; this defect may play a role in increased renal sympathetic nerve activity and in the development or maintenance of hypertension in SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID