NONO2P, a nitric oxide donor, induces relaxation in coronary artery, negative inotropism and hypotensive effect in...

Reduced NO synthesis and/or bioavailability is related with many cardiovascular diseases, such as coronary artery disease and hypertension. This study aimed to evaluate the effects of cis-[Ru(NO)(NO2)(phen)2](PF6)2-(NONO2P) on blood pressure in normotensive and hypertensive rats. Specifically, we wanted to investigate its action on the atrial contractility, mesenteric and coronary arteries function. Male Wistar and spontaneously hypertensive rats (SHR) (13-18 weeks old) were used to assess the NONO2P effects on blood pressure and heart rate. Superior mesenteric and coronary arteries, and atria were isolated for recording to analyze force changes. Cultured endothelial cells were used to measure intracellular reactive oxygen species (ROS) generation using fluorescent dye (dihydroethidium, DHE). Acute administration of NONO2P induced hypotension in non-anesthetized normotensive and hypertensive rats. Moreover, NONO2P caused a negative inotropic effect without altering cardiac rhythmicity. Further, NONO2P displays a vasorelaxant effect on different blood vessels (mesenteric and coronary arteries). For comparison purposes, we observed that NONO2P and NTG presented with a similar potency and maximum response values in inducing relaxation in coronary arteries. On the other hand, mesenteric arteries were more sensitive to both donors, NONO2P and NTG, than the coronary artery. In addition, exposure to NONO2P induced tolerance and increased ROS levels. This is the first evidence that NONO2P induces hypotension, negative cardiac inotropism and coronary artery relaxation. In addition, pre-exposure to NONO2P induces vascular tolerance. Overall, these results may shed light on the potential therapeutic use of NONO2P, particularly in treating angina and hypertensive crises.