Influence of blood gases, Ca2+-entry blockade and angiotensin converting enzyme inhibition on pressor responses to alpha-adrenoceptor agonists: evidence in vivo for subtypes of response independent of receptor subtype?
The pressor responses in the pithed rat to alpha-adrenoceptor agonists can be modified by alterations in arterial blood gas levels or by drugs which interfere with excitation-contraction coupling processes in the vascular smooth muscle, e.g. Ca2+-entry blockers or angiotensin converting enzyme (ACE) inhibitors. However, the extent of these influences depends on which agonist is used. The pressor response to intravenous injection of alpha-adrenoceptor agonists consists of two phases: an initial rapid but transient response (phase I) is followed by a response of slower onset but longer duration (phase II). We have examined the effects of manipulation of arterial blood gases, a Ca2+-entry blocker, nifedipine, and an ACE inhibitor, teprotide, on the pressor responses to a series of alpha-adrenoceptor agonists. In each case, the effects showed selectivity for one or other of the two phases and the differences in susceptibility between agonists could be explained by the relative sizes of the two phases in their responses. In general, phase II was more susceptible to alkalosis, nifedipine and teprotide, so that drugs in which this component predominated were more susceptible to these factors. In contrast there was no direct correlation with the receptor subtypes activated by the agonists.
O'Brien
J W
JW
Flavahan
N A
NA
Grant
T L
TL
McGrath
J C
JC
Marshall
R J
RJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood*; D004983:Ethanolamines / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood*; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013722:Teprotide / Q000494:pharmacology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014991:Xylazine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D004983:Ethanolamines; D009842:Oligopeptides; D002245:Carbon Dioxide; D010656:Phenylephrine; D014991:Xylazine; C016980:amidephrine; D013722:Teprotide; D009543:Nifedipine; D010100:Oxygen