Interactions between angiotensin II and alpha-adrenoceptor agonists mediating pressor responses in the pithed rat.
1. The aim of the study was to investigate the interactions between angiotensin II (AII) and adrenoceptor-mediated pressor responses in the pithed rat. Emphasis was placed on the effects of AII on blood pressure per se and the possibility of differential effects on alpha 1- and alpha 2-adrenoceptor-mediated pressor responses. 2. A low concentration of the angiotensin converting enzyme (ACE) inhibitor, teprotide (1 mg kg-1) lowered the resting diastolic blood pressure (BP) and attenuated only the second phase components of pressor responses to both alpha 1- and alpha 2-adrenoceptor agonists. Infusion of AII (50 ng kg-1 min-1) did not reverse the attenuating effect of teprotide and did not reliably restore the basal diastolic BP. 3. Although teprotide (10 mg kg-1) did not produce a greater fall in diastolic BP than did the low dose (1 mg kg-1), it attenuated the peak and second phase pressor responses to alpha 1- and alpha 2-adrenoceptor agonists but had no effect on pressor responses to AII or 5-hydroxytryptamine (5-HT). Infusion of AII reversed the effects of teprotide (10 mg kg-1) provided that rats were pretreated with flurbiprofen (5 mg kg-1), confirming that the depressor effects of the higher dose of teprotide are AII-dependent but that demonstration of this was complicated by products of cyclo-oxygenase. 4. The AII-receptor antagonist, saralasin (4 micrograms kg-1 min-1) attenuated alpha 1- and alpha 2-adrenoceptor-mediated pressor responses in a manner similar to that of teprotide (10 mg kg-1), suggesting that in this pithed rat model the alpha-adrenoceptor-mediated responses were selectively facilitated by endogenous AII. 5. Infusion of AII (50 ng kg-1 min-1) over a 60 min period did not produce a pressor response in the absence of other drugs but did facilitate pressor responses to alpha-adrenoceptor agonists. This confirms that AII can modulate alpha-adrenoceptor-mediated responses independently of basal blood pressure. 6. Overall the results indicate a facilitatory role for endogenous AII on alpha-adrenoceptor-mediated pressor responses. This is discussed in relation to the failure to demonstrate this convincingly under similar conditions on sympathetic nerve-mediated pressor responses.
Grant
T L
TL
Autonomic Physiology Unit, University of Glasgow.
McGrath
J C
JC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State / Q000503:physiopathology; D005480:Flurbiprofen / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D012504:Saralasin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013722:Teprotide / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D000804:Angiotensin II; D010656:Phenylephrine; D012701:Serotonin; D005480:Flurbiprofen; D013722:Teprotide; D012504:Saralasin; D009638:Norepinephrine