Sgd 101/75 is distinguished from other selective alpha 1-adrenoceptor agonists by the inhibition of its pressor responses by calcium entry blockade and vasodilatation in pithed rats and cats.
The vasopressor effects of the selective alpha 1-adrenoceptor agonist Sgd 101/75 (2-[2-methylindazol-4-imino]-imidazolidine HCl) were analyzed in pithed rats and cats. Vasodilatation by the beta 2-adrenoceptor agonist salbutamol (1 mg/kg i.v.) or by the converting enzyme inhibitor captopril (5 mg/kg i.v.) antagonized the vasoconstriction by Sgd 101/75 in pithed rats. The effect of salbutamol was abolished by restoration of the baseline diastolic pressure by infusion of vasopressin. Calcium entry blockade by nifedipine (0.1-3 mg/kg i.v.) and (-)-verapamil (0.3 and 1 mg/kg i.v.) dose dependently inhibited the rise in the diastolic pressure induced by Sgd 101/75 pithed rats. This inhibition could not be attenuated by an infusion of vasopressin. In pithed cats, nifedipine most effectively antagonized the pressor effects of Sgd 101/75. In this respect, Sgd 101/75 is different from other alpha 1-adrenoceptor agonists, which are known to elicit a vasoconstriction which is virtually insensitive to vasodilatory measures and calcium entry blockade. These findings may be explained on the basis of a further subdivision of vascular postjunctional alpha 1-adrenoceptors.
D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002415:Cats; D003000:Clonidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D009543:Nifedipine; D003000:Clonidine; C034204:indanidine; D000420:Albuterol