The vasodilatory effect of allopurinol mediates its antihypertensive effect: Effects on calcium movement and cardiac hemodynamics.

Despite the reported reduction in blood pressure in hypertensive patients treated with allopurinol, the mechanism of the allopurinol hypotensive effect is still unclear. In the current study, the hypotensive effect of allopurinol has been fully investigated in hypertensive rats. Hypertension was induced in rats by angiotensin II (120 ng/min/kg) infusion for two weeks. Rats were then subjected to real-time recording of blood pressure, left ventricular pressure and volume and surface ECG. After 10 min of basal recording, allopurinol was slowly injected into the femoral vein with a dose of 10 μmole/kg. Then, invasive blood pressure, cardiac hemodynamics and ECG were continuously recorded for an additional 20 min. In addition, the vasodilation effect of allopurinol was studied using the isolated artery technique. Allopurinol injection reduced systolic, diastolic and pulse blood pressure. Allopurinol suppressed both cardiac systolic and diastolic hemodynamics as is apparent from the reduction in the rate of rise and the rate of fall in left ventricular pressure. Allopurinol reduced the general cardiac output quickly. Allopurinol addition to the organ bath (10-1000 μM) produced significant vasodilation of PE pre-constricted aortae that was not affected by endothelium denudation, L-NAME or indomethacin. However, allopurinol ameliorated the calcium induced contraction of aorta pre-constricted with KCl in calcium-free media. Erk or ROCK inhibition did not attenuated allopurinol produced vasodilation. In conclusion, allopurinol has an antihypertensive effect that is mediated, probably, by reducing cardiac output and decreasing vascular resistance. The vasodilator effect of allopurinol is most likely mediated by calcium blocking activities.