Sex Differences in the Biomechanics and Contractility of Intramural Coronary Arteries in Angiotensin II–Induced Hypertension

Abstract

It is well known that sex differences occur in both the pathogenesis and therapy of hypertension. A deeper understanding of the underlying processes may be helpful when planning a personalized therapeutic strategy. In laboratory animal experiments, we studied the early mechanisms of vascular adaptation of the intramural small coronary arteries that play a fundamental role in the blood supply of the heart. In our study, an osmotic minipump was implanted into 10 male and 10 female Sprague-Dawley rats. The pump remained in situ for 4 weeks, infusing a dose of 100 ng/kg/min angiotensin II acetate. Four weeks later, the animals were killed, and the intramural coronary arteries from the left coronary branch, which are fundamentally responsible for the blood supply of the heart, were prepared. The pharmacologic reactivity and biomechanical properties of the prepared segments were studied in a tissue bath. The relative heart mass and vessel wall thickness were greater in females than males (0.387 [0.009] g/100 g vs 0.306 [0.006] g/100 g body weight; 41.9 [4.09] μm vs 33.45 [3.37] μm on 50 mm Hg). The vessel tone and vasoconstriction in response to thromboxane agonists were, however, significantly more pronounced in males. The extent of relaxation in response to bradykinin was also greater in females. Although we observed inward eutrophic remodeling in females, an increase in wall stress and elastic modulus dominated in males. The early steps of angiotensin II-dependent hypertension evoked very different adaptation mechanisms in males and females.