Induction of opposite response of hindlimb vasculature to adrenergic agents in hypothyroid rats.
In order to investigate whether hypothyroidism induces some functional change in the vascular smooth muscle, the responsiveness of the femoral vascular bed of hypothyroid rats to vasoactive agents was compared with that of euthyroid rats. The vascular beds were perfused by using the constant flow method. Ad libitum feeding of 0.15% 6-propylthiouracil to young male Wistar rats (120 g) over 3 months leads to hypothyroidism. Hypothyroidism did not induce any changes in the Ach- or papaverine-induced vasodilation and 5-HT-induced vasoconstriction. In contrast to euthyroidism, hypothyroidism induces a marked augmentation of the clonidine-induced vasoconstriction, while the phenylephrine-induced vasoconstriction and isoprenaline-induced vasodilation were clearly attenuated. The response to phenylephrine in euthyroidism was predominantly inhibited by prazosin and was slightly modified by yohimbine. While the attenuated response to phenylephrine in hypothyroidism was modified by these blockers in a converse manner, the response to clonidine in each rat group was not modified by prazosin, but markedly inhibited by yohimbine. From these results the following conclusions were obtained: both alpha-1 and alpha-2 adrenoceptors in the femoral vascular beds of eu- and hypothyroid rats responded to phenylephrine; phenylephrine stimulated predominantly alpha-1 adrenoceptors in euthyroidism; hypothyroidism caused an attenuation of the responsiveness mediated through alpha-1 adrenoceptors and an augmentation of that of alpha-2 receptors; hypothyroidism caused an opposite response, mediated through alpha- and beta-receptors, without influencing muscarinic and serotoninergic responses; augmentation of the alpha-2 response and attenuation of alpha-1 and beta-2 responses caused by hypothyroidism may be attributed to functional changes at receptor sites.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D007037:Hypothyroidism / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010208:Papaverine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013566:Sympathomimetics / Q000494:pharmacology*
D013566:Sympathomimetics; D010208:Papaverine; D007545:Isoproterenol; D003000:Clonidine; D000109:Acetylcholine; D011224:Prazosin