ADDITIVE DAMAGE IN THE CONTRACTILITY OF INTRAMURAL CORONARY ARTERIOLES IN A RAT MODEL OF ANDROPAUSAL HYPERTENSION

Abstract

Objective: Hypertension accelerates vascular aging, and changes associated with vascular aging play a role in hypertension. Andropause also contributes to age – related vascular damage and increases cardiovascular risk. Our aim is to investigate the combined effect of hypertension and androgen deficiency on the contractility of intramural coronary resistance arteries. Design and method: Male Sprague-Dawley rats were distributed into 4 groups: control (Co, n = 10); orchidectomized (OCT, n = 13), angiotensin II infused (AII, n = 10) and AII infused plus orchidectomized (AII+OCT, n = 8). Early hypertension was established using osmotic minipumps containing angiotensin II (100 ng / min / kg), while testosterone deficiency achieved via orchidectomy. After 4 weeks, spontaneous, thromboxane- and bradykinin-induced tones of intramural coronary resistance arterioles were investigated by in vitro pressure microarteriography. Results: Inner radius was reduced in the AII+OCT group compared to all other groups. Spontaneous tone was significantly higher in AII and AII+OCT groups than in Co and OCT groups. U46619-induced vasoconstriction was significantly smaller in OCT and AII+OCT groups compared to Co and AII rats. Bradykinin-induced relaxation was also significantly reduced in orchidectomized rats (OCT and AII+OCT groups) to a greater extent than in Co and AII animals. Conclusions: Spontaneous vascular tone is increased in AII hypertension. As a result of orchidectomy, adaptation range of the blood vessels narrows both regarding vasoconstriction and vasodilation. Therefore, the reactivity of the coronary arterioles deteriorates due to testosterone deficiency. In case of parallel manifestation of hypertension and testosterone deficiency, these two effects add up, which may increase age-related cardiovascular risk significantly in men.