Interactions between angiotensin II, sympathetic nerve-mediated pressor response and cyclo-oxygenase products in the pithed rat.

Abstract:

:1. The influence of angiotensin II (AII) on resting blood pressure and on sympathetic nerve-mediated pressor responses in the pithed rat was investigated either by inhibiting the renin-angiotensin system or by infusing AII. 2. Plasma AII levels in the pithed rat were approximately 20 fold higher than in normotensive rats. 3. Infusion of a subpressor dose of AII (50 ng kg-1 min-1) had no effect on sympathetic nerve mediated pressor responses but a pressor dose of AII, (200 ng kg-1 min-1) facilitated nerve-mediated pressor responses. 4. The angiotensin converting enzyme inhibitor, teprotide, and the AII-receptor antagonist, saralasin, lowered the diastolic blood pressure and attenuated sympathetic nerve-mediated pressor responses. There was no difference in the effects of teprotide at 1 mg kg-1 and 10 mg kg-1. Infusion of sodium nitroprusside at concentrations producing a fall in diastolic blood pressure of similar magnitude to that produced by teprotide and saralasin significantly attenuated nerve-mediated pressor responses. 5. After teprotide, AII 50 mg kg-1 min-1 increased diastolic blood pressure. The inhibitory effect of teprotide on nerve-mediated pressor responses was antagonized by this infusion of AII only if the rats were pretreated with the cyclo-oxygenase inhibitor, flurbiprofen. 6. It is concluded that AII is a major determinant of vascular tone in the pithed rat and that inhibition of the renin-angiotensin system attenuates sympathetic nerve-mediated pressor responses at least in part through the fall in blood pressure per se. The demonstration of this is complicated by an excessive release of vasodilator prostaglandins possibly due to the infused AII. Since plasma All levels are high, the effects of blockade of the renin-angiotensin system will be exaggerated and so the importance of All as a modulator of sympathetic responses will be overestimated in this model.

journal_name

Br J Pharmacol

authors

Grant TL,McGrath JC

doi

10.1111/j.1476-5381.1988.tb11759.x

subject

Has Abstract

pub_date

1988-12-01 00:00:00

pages

1220-8

issue

4

eissn

0007-1188

issn

1476-5381

journal_volume

95

pub_type

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