Interactions between angiotensin II and α‐adrenoceptor agonists mediating pressor responses in the pithed rat

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Abstract
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 α1 and α2‐adrenoceptor‐mediated pressor responses. A low concentration of the angiotensin converting enzyme (ACE) inhibitor, teprotide (1 mgkg−1) lowered the resting diastolic blood pressure (BP) and attenuated only the second phase components of pressor responses to both α1‐ and α2‐adrenoceptor agonists. Infusion of AII (50ngkg−1 min−1) did not reverse the attenuating effect of teprotide and did not reliably restore the basal diastolic BP. Although teprotide (10mgkg−1) did not produce a greater fall in diastolic BP than did the low dose (1mgkg−1), it attenuated the peak and second phase pressor responses to α1 and α2‐adrenoceptor agonists but had no effect on pressor responses to AII or 5‐hydroxytryptamine (5‐HT). Infusion of AII reversed the effects of teprotide (10mgkg−1) provided that rats were pretreated with flurbiprofen (5mgkg−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. The AII‐receptor antagonist, saralasin (4μgkg−1 min−1) attenuated α1‐ and α2‐adrenoceptor‐mediated pressor responses in a manner similar to that of teprotide (10mgkg−1), suggesting that in this pithed rat model the α‐adrenoceptor‐mediated responses were selectively facilitated by endogenous AII. Infusion of AII (50ngkg−1 min−1) over a 60min period did not produce a pressor response in the absence of other drugs but did facilitate pressor responses to α‐adrenoceptor agonists. This confirms that AII can modulate α‐adrenoceptor‐mediated responses independently of basal blood pressure. Overall the results indicate a facilitatory role for endogenous AII on α‐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.

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