Alpha 1-adrenoceptor reserve and effects of a Ca2+ entry blocker (Ro 18-3981) on aorta of spontaneously hypertensive rats.
The relationship between alpha 1-adrenoceptor reserve and the sensitivity of vasoconstrictor responses to Ca2+ entry blockade was investigated in isolated aortas from age-matched (13-15 weeks) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Noradrenaline (NA) elicited contractile responses with a greater potency (log EC50) in aorta from WKY (-8.7) than in those from SHR (-8.05). The dihydropyridine Ca2+ entry blocker, Ro 18-3981 (10(-6) M), suppressed the maximal NA responses more in aorta of SHR (-54%) than WKY (-14%). The dissociation constant (KA) of NA was similar in aortas of both strains. However, the difference between KA and EC50 values was greater in aorta of WKY (7.2 X) than in those from SHR (1.4 X). Pretreatment of WKY aorta with the irreversible alpha-blocker phenoxybenzamine (10(-9) M) enhanced the inhibitory effect of Ro 18-3981 (10(-6) M) against NA-induced contractions (-14 to -47%). Thus, a smaller alpha 1-adrenoceptor reserve could explain the greater sensitivity of NA-induced contractions in SHR aorta to Ca2+ entry blockade.
Holck
M I
MI
Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd., Basle, Switzerland.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; C052934:Ro 18-3981; D015016:Yohimbine; D009638:Norepinephrine; D011224:Prazosin