Calcium-dependence and antagonism of responses to alpha 1- and alpha 2-adrenoceptor agonists in vascular tissues from hypertensive and normotensive rats.
Inhibition by D600 (methoxyverapamil) of responses to an alpha 2-adrenoceptor selective agonist, B-HT 920, (6-allyl-2-amino-5, 6, 7, 8-tetrahydro-4H-thiazolo [4, 5-d] azepin dihydrochloride), an alpha 1-adrenoceptor selective agonist, phenylephrine (PE), and a nonselective agonist, noradrenaline (NA), was studied in isolated preparations of the aortae and carotid arteries obtained from young (5-7 weeks) and old (15-17 weeks) hypertensive (SHR) and normotensive (WKY) rats. Maximum responses of WKY tissues to B-HT 920 were the most sensitive, PE-induced responses the least sensitive and maximum responses to NA were intermediate in their sensitivity to inhibition by D600. Sub-maximal responses to NA and PE were not different in their sensitivity to inhibition by D600, but were less sensitive than the responses to B-HT 20. Sub-maximal responses to PE were significantly more sensitive to D600 inhibition than were the maximal responses to this agonist. NA-induced responses of tissues from older SHR were less sensitive to inhibition by D600 when compared to responses in WKY rats. Responses to B-HT 920, in tissues suspended in calcium-free solutions, showed the largest decline compared to NA- and PE-induced responses. We conclude that responses to B-HT 920 largely utilize extracellular calcium. PE- and NA- induced responses mobilize extracellular calcium to varying degrees depending upon the concentration of the agonist employed to elicit the response.
D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D002339:Carotid Arteries / Q000187:drug effects; D005711:Gallopamil / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D010656:Phenylephrine; D005711:Gallopamil; C024763:talipexole; D002118:Calcium; D009638:Norepinephrine