Exercise and vasorelaxing effects of CO-releasing molecules in hypertensive rats.

Purpose: Because carbon monoxide (CO) has been reported able to induce relaxation, we aimed to investigate the effects of exercise training on the rat thoracic aorta responsiveness to a CO-releasing molecule (CORM), tricarbonyldichlororuthenium ([Ru(CO)3Cl2]2).

Methods: Male Wistar rats (N = 32) were divided in hypertensive and normotensive groups using the two-kidney, one-clip model of Goldblatt or SHAM surgery. Hypertensive and normotensive groups were assigned to an exercise training protocol on a level treadmill over a 10-wk period or were assigned to remain sedentary. After the exercise training protocol, blood pressure and cardiac tissue weight were assessed. The responsiveness of endothelium-denuded thoracic aortic rings to [Ru(CO)3Cl2]2 was evaluated by isometric contractions recordings.

Results: Systolic, diastolic, and mean blood pressures were significantly increased in hypertensive rats compared with control rats. Exercise training did not significantly alter blood pressure but decreased pulse pressure in hypertensive animals compared with sedentary hypertensive rats. In all groups, application of [Ru(CO)3Cl2]2 induced relaxation in precontracted aortic rings. Compared with normotensive rats, CO-induced relaxation was significantly decreased in hypertensive rats. Nevertheless, training exercise increased relaxation markedly in response to [Ru(CO)3Cl2]2 application in hypertensive rats, whereas it remained without effect in control rings. Pretreatment with TEA, a nonselective K+ channel inhibitor, decreased [Ru(CO)3Cl2]2-induced relaxation in all groups that became similar. In trained hypertensive rats, iberiotoxin had effects similar to those of TEA.

Conclusions: This finding supports the concept that the CORM [Ru(CO)3Cl2]2 can induce relaxation in both normotensive and hypertensive rats with an impairment of the CO-induced relaxation during hypertension. However, exercise training improves the aorta's ability to relax in response to [Ru(CO)3Cl2]2 during hypertension, probably by increasing K+ channel activity.