Microvascular resistance (MVR), determined as the ratio of the second-order arteriolar blood pressure (servo-null method) to blood flow (dual-slit), was assessed in the cremaster muscle preparation of 7- to 8-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The MVR was used as an index of resistance during 1) control conditions; 2) superfusion of graded concentrations of the catecholamine norepinephrine (NE; WKY n = 8, SHR n = 8); 3) superfusion with NE and in the presence of a fixed concentration of the vasodilator sodium nitroprusside (NP; 10(-5) M); and 4) superfusion with the noncatecholamine phenylephrine (PE; WKY n = 8, SHR n = 9). The vasoconstrictor challenges were carried out to determine if there was any differential vascular sensitivity between the hypertensive and nonhypertensive rats to the exposure of an endogenous-like constrictor possessing a catechol nucleus as opposed to a strictly synthetic analog. The presence of NP was employed to assess the degree of vasoconstriction normally present under control conditions. The combination of NE and NP was used to test for a differential vasoconstrictor sensitivity, beginning from maximally dilated conditions. The MVR, assessed at the second-order arteriolar level, represents approximately 35% of the total resistance of the skeletal muscle and is intimately involved in maintaining proper end-organ perfusion pressure. The microvascular resistance of the SHR group was almost four times greater than that of the WKY group under control conditions. Maximum vasodilation with topical NP reduced the MVR in both groups, but the SHR microvascular resistance remained two times greater than that found in the WKY. The SHR had greater MVR responses following challenge with both NE and PE and also in the presence of NP during NE challenge. The conclusions are: 1) the microvascular resistance of the SHR is elevated under control conditions due to structural modifications of the vasculature and exacerbated following constrictor challenge as a result of heightened vasoconstrictor sensitivity; and 2) the elevated MVR in the SHR is not due to a simple arterial vasoconstriction that can be totally eliminated with vasodilation.