Adrenergic receptors and increased reactivity of aortic smooth muscle in renal hypertensive rats.
The contractile responses of aortic smooth muscle and the dissociation constant (Ka) of the norepinephrine (NE) acting on alpha-adrenergic receptors in isolated thoracic aorta from normotensive and renal hypertensive rats were studied. Male Wistar rats were made hypertensive by uninephrectomy with figure-of-eight ligatures around the contralateral kidney. Two to three weeks after operation, the arterial systolic pressure for sham-operated rats was 123 +/- 2, and that for hypertensive rats was 164 +/- 4 mm Hg. Spontaneous rhythmic contractions of aortic rings, which were potentiated by low [Na]o and abolished by nifedipine (10(-6) - 10(-5) M), were observed in 4 out of 18 hypertensive rats. Aortic rings from normotensive rats showed no spontaneous rhythmicity. Although rhythmic phasic contractions could be induced in normotensive tissues by NE or caffeine in the presence of NE, tissues of hypertensive rats responded more readily. Furthermore, the threshold and the ED50 for tonic contractile response to NE was lower in hypertensive aortic rings than in the rings obtained from normotensive aortas. The Ka of NE acting on alpha-adrenergic receptors was derived from concentration-response data for NE before and after irreversible blockade of a fraction of the receptors with dibenamine (1-2 X 10(-7) M) in the presence of cocaine and propranolol. Mean Kas obtained were 5.58 +/- 0.42 X 10(-7) and 2.12 +/- 0.28 X 10(-7) M for normotensive and hypertensive rats, respectively. The increased contractile responses of the hypertensive aorta may be explained, at least partially, by a higher resting [Ca]i and a greater affinity of NE acting on the alpha-adrenergic receptors.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006977:Hypertension, Renal / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D002110:Caffeine; D012964:Sodium; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine