Despite in vitro increase in cyclic guanosine monophosphate concentrations, intracarotid nitroprusside fails to augment cerebral blood flow of healthy baboons

Abstract

Background: During Cerebr. angiography, intracarotid infusion of sodium nitroprusside (SNP), an endothelium-independent nitric oxide donor, fails to increase Cerebr. blood flow (CBF) of Hum. subjects. A confounding effect of intracranial Pathol. or that of radiocontrast could not be ruled out in these experiments. The authors hypothesized that, if nitric oxide was a significant regulator of CBF of primates, then intracarotid SNP will augment CBF of baboons. Methods: In in vivo studies, CBF (intraarterial 133Xe technique) was measured in healthy baboons during isoflurane anesthesia at (1) baseline/during (2) induced hypertension with intravenous phenylephrine, (3) concurrent infusions of intravenous phenylephrine/intracarotid SNP,/(4) intracarotid verapamil (positive Ctrl. drug). In in vitro studies, the authors measured tissue cyclic guanosine monophosphate (cGMP) by radioimmunoassay after incubating vascular rings obtained from freshly killed baboons (1) with increasing concentrations of SNP and (2) after SNP exposure following preincubation with the radiocontrast agent, iohexhol. Results: In the in vivo studies, coinfusion of intravenous phenylephrine and intracarotid SNP did not increase CBF. However, intracarotid verapamil significantly increased CBF (from 26 ± 7 to 43 ± 11 ml · 100 g-1 · min-1; P < 0.0001) without a change in mean arterial pressure. In the in vitro studies, incubation of intracranial arterial rings in SNP resulted in dose-dependent increases in cGMP concentrations. A similar increase in cGMP content was evident despite iohexhol preincubation. Conclusions: Collectively, these results suggest that, in healthy baboons, intracarotid SNP does not decrease arteriolar resistance, although SNP could affect proximal arterial tone, as demonstrated by the in vitro increase in cGMP content of these vessels.