The long term objective of the proposed work is to determine the cause for the changes in arterial mechanical properties which result in increased resistance to blood flow in hypertension. If these changes are known then studies on treatment of hypertension can be directed at the mechanism for mechanical properties that have been altered.
The specific aims of this application are to show that: 1.) Arterial wall damage in the early phase of hypertension can cause a variety of mechanical changes which include increased distensibility and viscosity of the wall tissue, decreased force of contraction from smooth muscle cells, and/or increased tone. 2.) After the initial rise in pressure the vessel wall responds by decreasing its distensibility and/or increasing its thickness without a change in sensitivity or contractility of smooth muscle cells. 3.) Measurement of sensitivity and thickness depends on vessel diameter or the length imposed on in vitro specimens. This can result in apparent changes of these properties with hypertension and 4.) Compensatory changes in thickness and distensibility will occur first in large arteries which will protect the smaller vessels from the higher pressure. As the pressure continues to increase in hypertension the compensatory response will occur in progressively smaller vessels. The methodology for achieving these goals includes: 1.) Distensibility changes will be characterized by a stress-strain relationship in the resting vessel and by a stress-strain relationship of the series elastic element in the stimulated vessel. Changes in viscosity of the arterial wall will be characterized by a stress relaxation relationship. Experimental parameters will be obtained from a unified viscoelastic theory that describes both stress-strain and relaxation. 2.) Contractility will be characterized by a force-velocity relationship and a length-tension relationship. Force-velocity experiments will provide parameters for a hyperbolic relationship as well as the series elastic element stress-strain relationship. Differences in certain characteristics of the length-tension relationship that are due to agonist concentration will be accounted for. 3.) Vessel wall thickness measurements will be done on-line with a video technique and with chemically fixed specimens. In both studies the effect of vessel circumference will be accounted for and 4.) These experiments will use the renovascular hypertensive dog and rat and the spontaneously hypertensive rat. Studies on the progression of the compensatory response from large vessels to small vessels will be done in renovascular hypertensive rats and dogs.
