Spinal nitric oxide participates in the control of the blood pressure during graded hemorrhage in the conscious rat.

Abstract

We sought to evaluate the role of spinal nitric oxide (NO) in the control of blood pressure in the conscious animal and determine its possible participation in the progression of hemorrhagic shock. Adult, male Sprague-Dawley rats were chronically prepared with intrathecal, intravenous, and intra-arterial catheters. We first investigated the role of spinal NO on blood pressure control by intrathecal administration of N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) at 0.37 micromol, 0.74 micromol. or 1.48 micromol. A dose-related increase in blood pressure was observed. We next pretreated animals with intrathecal or intravenous L-NAME at 0.37 micromol and induced the animal to shock by graded hemorrhage. Animals that received vehicle control or intravenous L-NAME had a decrease in blood pressure after 12% of the total circulatory blood volume (TBV) had been removed and developed severe hypotension after 24% TBV was bled. On the other hand, intrathecal pretreatment of L-NAME significantly attenuated the decrease in blood pressure. The blood pressure was maintained until 40% TBV had been withdrawn. We concluded that inhibition of NO synthase, in the spinal cord, increased blood pressure in a dose-dependent manner, and hemorrhagic shock induced by graded hemorrhage may involve an upregulation mechanism of spinal NO synthase in producing severe hypotension in conscious rats.