title: Despite in vitro increase in cyclic guanosine monophosphate concentrations, intracarotid nitroprusside fails to augment cerebral blood flow of healthy baboons.
abstract: BACKGROUND
  During cerebral angiography, intracarotid infusion of sodium nitroprusside (SNP), an endothelium-independent nitric oxide donor, fails to increase cerebral blood flow (CBF) of human subjects. A confounding effect of intracranial pathology 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 studies, CBF (intraarterial (133)Xe technique) was measured in healthy baboons during isoflurane anesthesia at (1) baseline and during (2) induced hypertension with intravenous phenylephrine, (3) concurrent infusions of intravenous phenylephrine and intracarotid SNP, and (4) intracarotid verapamil (positive control drug). In 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 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 x 100 g(-1) x min(-1); P < 0.0001) without a change in mean arterial pressure. In the 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 increase in cGMP content of these vessels.
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA. sj121@columbia.edu
authors.forename: Shailendra
authors.initials: S
authors.lastname: Joshi
authors.forename: Roger
authors.initials: R
authors.lastname: Hartl
authors.forename: Lena S
authors.initials: LS
authors.lastname: Sun
authors.forename: Adam D
authors.initials: AD
authors.lastname: Libow
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Pile-Spellman
authors.forename: William L
authors.initials: WL
authors.lastname: Young
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
authors.forename: Carol A
authors.initials: CA
authors.lastname: Hirshman
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002343:Carotid Artery, Internal; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism*; D066298:In Vitro Techniques; D007269:Injections, Intra-Arterial; D007472:Iohexol / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D010215:Papio; D014665:Vasodilator Agents / Q000494:pharmacology*; D014980:Xenon Radioisotopes
chemical_list: D014665:Vasodilator Agents; D014980:Xenon Radioisotopes; D009599:Nitroprusside; D007472:Iohexol; D006152:Cyclic GMP