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Changes in arterial smooth muscle contractility, contractile proteins, and arterial wall structure in spontaneous
1Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202-5120.
Insights
Essential hypertension may stem from defective arterial smooth muscle contractility. Studies show altered muscle mechanics in hypertensive rats, suggesting a primary defect contributing to increased total peripheral resistance and high blood pressure.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Hypertension Research
Background:
- Essential hypertension is a major risk factor for heart disease, stroke, and kidney failure.
- The precise initiating mechanism of essential hypertension remains unknown.
- Increased total peripheral resistance (TPR) is a recognized hemodynamic hallmark of essential hypertension.
Purpose of the Study:
- To investigate the hypothesis that increased TPR in essential hypertension is caused by defective arterial smooth muscle contractility.
- To examine the mechanical properties of arterial smooth muscle in spontaneously hypertensive rats (SHR) compared to normotensive controls.
- To assess the role of structural vascular changes in hypertension.
Main Methods:
- Force-velocity and length-tension studies on arterial smooth muscle from SHR and Wistar-Kyoto rats (WKY).
- Mechanical behavior analysis of arterial muscle from SHR treated with MK-421 (enalapril maleate), an angiotensin-converting enzyme blocker.
- Morphometric analysis of mesenteric resistance arteries from SHR, MK-421-treated SHR, and WKY.
- Comparison of caudal arterial myofibrillar ATPase activities between SHR and WKY.
Main Results:
- SHR arterial muscle exhibited faster shortening velocity, greater shortening ability, and slower relaxation rates compared to WKY.
- MK-421 treatment normalized blood pressure in SHR but did not alter the intrinsic mechanical properties of their arterial muscle.
- MK-421-treated SHR showed reduced medial thickness and fewer smooth muscle cell layers in mesenteric arteries, similar to WKY.
- Increased actomyosin ATPase activity in SHR arterial muscle was investigated as a potential contributor to enhanced shortening velocity.
Conclusions:
- Defective arterial smooth muscle contractility is a likely primary contributor to increased TPR in essential hypertension.
- Structural vascular changes, such as medial thickening, may be a consequence rather than a cause of hypertension.
- Further research is warranted to fully elucidate the mechanisms underlying altered arterial smooth muscle function in 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. Light micrograph observations and morphometric analyses were made of cross-sections of mesenteric resistance arteries from SHR, MK-421-treated SHR, and WKY. Results show that the MK-421-treated SHR resistance arteries had media thicknesses and a number of smooth muscle cell layers that were significantly less than in the untreated SHR and not different from the WKY. Secondly, velocity of shortening is dependent on actomyosin ATPase activity, and, since maximum velocity of shortening has been shown to be increased in SHR arterial muscle, it became necessary to know whether or not an increased actomyosin ATPase activity might be responsible. Therefore, data from a study of SHR and WKY caudal arterial myofibrillar ATPase activities are compared.(ABSTRACT TRUNCATED AT 400 WORDS)