Changes in Arterial Smooth Muscle Contractility, Contractile Proteins, and Arterial Wall Structure in Spontaneous Hypertension

Abstract Heart disease, stroke, and kidney failure are leading causes of death. Essential hypertension is the major predisposing risk factor of cardiovascular disease. Yet, after several decades of intensive investigation, the initiating causative mechanism of essential hypertension is still unknown. However, investigators in the field generally agree that an increased total peripheral resistance (TPR) is the fundamental hemodynamic disorder in essential hypertension. This review addresses the hypothesis that the increased TPR of essential hypertension is due to a defective mechanism in the contractility of arterial smooth muscle. Force-velocity and length-tension studies have shown that both caudal arterial muscle and mesenteric resistance arterial muscle from spontaneously hypertensive rats (SHR) can shorten more and faster than muscle from normotensive control Wistar-Kyoto rats (WKY). In addition, the SHR muscle relaxation rate is slower compared with the WKY muscle. These alterations in mechanical behavior of SHR arterial muscle appear to be primary to the high blood pressure since MK-421 (enalapril maleate)-treated SHR arterial muscle shows the same increased velocity of shortening, increased shortening ability, and decreased relaxation rate as the untreated SHR muscle. MK-421 is an angiotensin-converting enzyme blocker. SHR maintained on MK-421 treatment have normal blood pressures in spite of being of the genetically hypertensive strain. While these findings are encouraging, several other important issues supporting the hypothesis require resolution and warrant review. Firstly, structural alterations of blood vessel walls in hypertension cause the walls to thicken and encroach on the vessel lumens contributing to the Increased TPR. Whether such wall thickening is the cause or consequence of high blood pressure has been controversial in the literature. In this report, data are presented from a study in which MK-421-treated SHR were utilized as a model of prehypertensive SHR.