Increased vasodilator responses to acetylcholine in psychosocial hypertensive mice.
Responsiveness to endothelium-dependent (acetylcholine and A23187) and endothelium-independent (nitroprusside and 8-bromo cyclic guanosine 3',5'-monophosphate [cGMP]) vasodilators was examined in two vascular preparations from hypertensive and normotensive mice. CBA Agouti mice were made hypertensive by exposure to social stress in a complex population cage. After 2 months, the hindquarter vascular bed was pump-perfused at a constant flow with plasma substitute to evaluate changes in perfusion pressure, and helical strips of aorta were suspended in muscle baths for measurement of isometric force generation. Tissues were treated with methoxamine to induce contractile tone. Threshold dilator responses to acetylcholine were elicited at a significantly lower dose in the hindquarters of hypertensive mice than in those from normotensive mice, indicating increased vasodilator sensitivity. In contrast, vasodilator responsiveness to nitroprusside in hindquarters of hypertensive mice did not differ from that in hindquarters of normotensive mice. Aortas from hypertensive mice were more sensitive (lower ED50) to the relaxant effects of acetylcholine and A23187 than those from normotensive mice. The relaxant effects of nitroprusside and 8-bromo cGMP on aortas from hypertensive mice were not significantly different from those in normotensive aortas. Aortic strips that had been rubbed on the lumen surface with a wooden stick did not relax to acetylcholine or A23187. In aortas that were not initially contracted with methoxamine, acetylcholine and A23187 caused small contractions from baseline. The magnitude of these contractile responses were potentiated after removal of the endothelium, and the potentiation was greater in aortas from hypertensive mice. These results demonstrate an increased responsiveness to endothelium-dependent vasodilators in this psychosocial model of hypertension.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D003441:Crowding / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide; D009599:Nitroprusside / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D000001:Calcimycin; D006152:Cyclic GMP; D008729:Methoxamine; D000109:Acetylcholine