The potential role of matrix metalloproteinases on reducing small artery stiffness and improving vasodilation in old spontaneously hypertensive rats

Abstract

Arterial stiffening is a major risk factor for cardiovascular disease development and progression. Both hypertension and aging are associated with presence of microcirculation endothelial dysfunction, hypercontractility, and vascular stiffening. Reports suggest that while hypertension results in inward remodeling, aging is associated with either no changes in internal diameter or outward remodeling with or without increases in wall thickness. Herein, we hypothesized that small arteries from old spontaneously hypertensive rats (SHR) would be inwardly remodeled and stiffer than old normotensive Wistar Kyoto (WKY) rats due to aggravated endothelial dysfunction, hypercontractility, and an increased presence of vascular smooth muscle stress fibers and collagen to elastin ratios. We further hypothesized that these characteristics would be associated with reduced expression of matrix metalloproteinases (MMPs). These hypotheses were tested in mesenteric arteries isolated from 88-week-old SHR and WKY rats. All reported differences are significant at P<0.05. SHRs had increased mean arterial pressure (P), pulse P, and heart weight normalized to body weight vs WKY rats. No differences in small mesenteric artery responses to phenylephrine or acetylcholine were observed between the rat strains. However, responses to the sodium nitroprusside were greater in SHR than in WKY isolated arteries. SHR arteries also had increased wall thickness and wall to lumen ratios, in addition to reduced cross-sectional compliance at 5-40 mmHg intraluminal P and lesser incremental modulus of elasticity at 80-120 mmHg. No differences in content of the extracellular matrices, collagen or elastin, were observed between arteries from either strain, whereas smooth muscle F-actin stress fibers were more abundant in the SHR arteries and MMP-2 and -9 expression were increased in the SHR arteries. In conclusion, these data suggest the interaction of age and hypertension in SHRs is associated with hypertrophic remodeling and increased responsiveness to nitric oxide likely due to increased MMP activity and reduced arterial stiffness. NIH HL-088105-02 to LAM-L This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.