Sodium nitroprusside-induced hypotension in dogs. Drug sensitivity and resistance experimentally provoked by circulating blood volume alterations.

The effects of small circulating blood volume alterations on the SNP dosage required to maintain the mean arterial pressure at 70 mm Hg were studied in 6 anesthetized dogs; (A) normovolemia, (B) hypovolemia by arterial bleeding 7 ml/kg, and (C) hypervolemia by infusing 7 ml/kg whole blood. The animals became extremely SNP sensitive during hypovolemia and resistant during hypervolemia (SNP dosage A: 25.8, B: 14.7, C: 70.0 microgram/kg/min); these changes were accompanied by significant changes in cardiac output (A: 193, B: 142, C: 249 ml/kg/min). The intravenous administration of SNP with the aim of inducing hypotension generally causes a balanced pre- and afterload reduction. This balance is rather delicate and easily disturbed by small intravascular fluid changes leading to cardiac output and thus to SNP sensitivity changes. Slowly developing tachyphylaxis can be explained on the basis of such intercompartimental fluid shifts and a case of SNP tachyphylaxis reported in literature is discussed on the basis of overinfusion. SNP tachyphylaxis or resistance might be treated by preload reducing measures like phlebotomy or the administration of nitroglycerin.