Changes in the effects of clonidine on left atrium and hindlimb vasculature of rats in various thyroid states. A study of the responsiveness of alpha 2-adrenoceptors in the cardiovascular system.
Postsynaptic alpha 2-adrenoceptors have been reported to exist in various tissues, including vascular smooth muscle. In order to investigate the possibility of their mediating a positive inotropic change and clarify the influence of the thyroid on their responsiveness, we examined the effects of clonidine, a known alpha 2-agonist, on the isolated left atria and femoral vascular beds of rats which were made hypo-, hyper- or euthyroid. Clonidine caused a dose-dependent positive inotropic change in the hypothyroid rat atrium, which was thought to be due to its alpha 1-stimulating action because of the antagonistic effect exerted by either phentolamine (10(-6) M) or prazosin (10(-7) M), but not by yohimbine (10(-7) M) or cimetidine (10(-5) M). In the hyperthyroid rat atrium, clonidine exerted a negative inotropic effect at high concentrations, which was thought to be due to its direct action on the cardiac muscle. Clonidine did not cause any inotropic change in the euthyroid rat atrium. Thus, an inotropic change mediated by the postsynaptic alpha 2-adrenoceptors could not be demonstrated in the rat heart. In the experiment involving hindlimb perfusion, clonidine caused vasoconstriction which was antagonized by yohimbine (10 micrograms/min). This effect was significantly augmented in the hypothyroid rats but not changed in the hyperthyroid ones. The vasoconstrictive effect of phenylephrine was found to be reduced in both hypo- and hyperthyroid rats. These results suggest that, in the peripheral vascular system, thyroid function also influences the postsynaptic alpha 2-adrenoceptors, but not in the same way as it affects the alpha 1-adrenoceptors.
D000818:Animals; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria; D006614:Hindlimb / Q000098:blood supply; D007037:Hypothyroidism / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D013961:Thyroid Gland / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; D003000:Clonidine; D010646:Phentolamine