PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE 180,62-71 (1985) Arteriolar and Systemic Autoregulatory Responses during the Development of Hypertension in the Spontaneously Hypertensive Rat (421 44)

Pressure-flow curves were constructed to determine whether acute autoregulation in rat skeletal muscle was altered during the development of hypertension in the spontaneously hypertensive rat (SHR). Under chlora1ose:urethane anesthesia, hindlimb blood flow and pressure, plus diameter changes of gacilis muscle arterioles, were simultaneously measured in the 6and 9-week Wistar-Kyoto (WKY) and SHR. Femoral blood flow was measured by electromagnetic flowmetry and hindlimb pressure controlled with an hydraulic occluder. Arteriolar diameters were measured using image shearing techniques. Acute autoregulatory capacity was assessed by comparing the closed-loop gain and the regression lines over the regulated and passive pressure ranges of the pressure-flow curves. The lower pressure limit of autoregulation (LPLAR) shifted upward as the blood pressure increased in the SHR with age: it did not shift in the WKY. Resting hindlimb flow, elevated in the SHR at 6 weeks, was also elevated at the LPLAR. At 9 weeks hindlimb blood flow was comparable in the WKY and SHR. As blood pressure was increased autoregulation was accompanied by vasoconstriction of gracilis arterioles. However, neither the gain of the autoregulatory system nor the regression lines describing the pressure-flow curves were different between the hypertensive and normotensive animals at either age. These results indicate that the acute autoregulatory response mechanism was not affected by the developing hypertension in the SHR, and is consistent with a structural basis for the chronic maintenance of the elevated peripheral vascular resistance. Q 198s Society for Experimental Biology and Medicine In several models of hypertension the onset of the blood pressure increase is characterized by normal peripheral vascular resistance, but a higher than normal cardiac output (1, 2). As the hypertension becomes established, long-term autoregulatory mechanisms act to restore cardiac output toward normal levels with the elevated blood pressure now being sustained by an elevated peripheral vascular resistance. The mechanisms underlying this long-term autoregulatory control may differ from those mediating acute autoregulatory responses. Local autoregulatory responses to acute changes in blood flow can be rapidly achieved by transient alterations in vessel caliber. Longterm autoregulatory responses to a prolonged increase in cardiac output may, however, occur more slowly and involve structural modifications of the microvasculature. For example, a rarefaction of resistance vessels has been demonstrated among various vascular beds of the spontaneously hypertensive rat (SHR) (3-8) and other models of hypertension (912), including untreated hypertensive patients (1 3). Because local autoregulatory mechanisms are active at the same level of the vascular tree as these reported structural changes (14), the possibility exists that such modifications of the microvasculature may alter the ability of a vascular bed to preserve normal acute autoregulatory function. Accordingly, experiments were conducted to determine whether the autoregulatory ability of skeletal muscle is affected during the developmental phase of spontaneous hypertension, and to assess further if these differences are correlated with an altered arteriolar responsiveness to changes in perfusion pressure. Local autoregulatory effectiveness was assessed in 6and 9-week spontaneously hypertensive rats by comparing the change in blood flow for a given change in arterial pressure (gain), and by comparing the regression lines of pressure-flow curves constructed at these two ages. A preparation utilizing the rat hindlimb was developed which permitted simultaneous