Saralasin dilates arterioles in SHR but not WKY rats

Microvascular responses to topical or intravascular saralasin were determined in the cremaster muscle arterioles of adult spontaneously hypertensive rats (SHR, n = 19) and Wistar-Kyoto (WKY, n = 16) normotensive rats. Animals were anesthetized with chloralose and urethane, and they breathed room air spontaneously. Mean arterial pressure was obtained from a catheter in a carotid artery, and microvascular diameters were determined by video microscopy. Plasma renin activity was measured in animals that were treated identically except that saralasin was not administered. For all animals, mean arterial pressure averaged 126 ± 4 mm Hg in SHR and 82 ± 4 mm Hg (p < 0.001) in WKY rats. Topical saralasin, 10"6 M, was applied to the cremaster muscles of SHR (n = 9) or WKY (n = 8) rats while internal diameters of first-through fourth-order arterioles (A 1, A2, A3, A4) were measured. Topical saralasin did not alter arteriolar diameters (Al through A4) in WKY rats, but A3 and A4 vessels dilated significantly (29% ± 5% and 38% ± 7% respectively; p < 0.01) in SHR, Fourth-order diameters were measured in other SHR (n = 10) and WKY (n = 8) rats while saralasin was administered intraarterially (300 μg bolus into the hypogastric artery) or intravenously (10 yag/kg/min for 30 minutes). Intraarterial or intravenous saralasin caused significant dilation (32% ± 12% and 20% ± 4%, respectively; p < 0.01) of A4 arterioles in SHR, but no dilation occurred in the arterioles of WKY rats. Arteriolar responses were significantly different (p < 0.001) in SHR vs WKY rats for both the topical and the intravascular administration of saralasin. Results demonstrated a functional difference in arteriolar responsiveness to saralasin in SHR vs WKY rats and imply that endogenous angiotensin exerts significant control on the muscle microvasculature in the SHR but not WKY rat. Results refute the hypothesis that saralasin is unable to reach a site of action in the vessel wall.