A Microvascular Site of Action of Sodium Nitroprusside in Striated Muscle of the Rat

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Abstract
The microvascular effects of sodium nitroprusside (SNP) were studied in rat striated muscle to determine the peripheral vascular sites of action of the drug. Eleven male rats were anesthetized with pentobarbital and the cremaster muscle was prepared for television microscopy. The internal diameters of 3 arterioles and 2 venules of each animal were measured before, during and after SNP infusion (40 .mu.g/kg per min). First-order arterioles (123 .+-. 7 .mu.m) showed no significant response to SNP and their internal diameters correlated poorly (r [correlation coefficient] = -0.31) with decreases in mean arterial pressure (MAP). The internal diameters of 3rd-order arterioles (42 .+-. 2 .mu.m) correlated well with MAP (r = 0.85) but these arterioles did not dilate significantly during SNP infusion. The internal diameters of 4th-order arterioles (15 .+-. 1 .mu.m) correlated best with MAP (r = 0.91) and significant (P < 0.05) throughout exposure to SNP. Both 3rd and 4th-order arterioles constricted significantly when SNP infusion was discontinued. Venular diameters are were not affected by SNP. In 5 additional rats, topical application of SNP (10-4 M) to the cremasteric microvasculature resulted in dilatation of 4th-order arterioles, which persisted throughout exposure to SNP, but reverted to control diameters when the drug was removed. The transient dilatation of some 4th-order arterioles and the arteriolar constriction observed when i.v. infusion of SNP was terminated appear to represent compensatory responses to hypotension, since these effects were not seen with topical application of SNP. The primary peripheral vascular site of action of SNP may be in 4th-order arterioles.