Effect of desmopressin acetate on hindlimb perfusion pressure in rats: what is the mechanism?
Desmopressin acetate (DDAVP) is a synthetic analogue of vasopressin used to promote hemostasis and reduce postoperative blood loss. Desmopressin acetate can cause hypotension in humans. Our study evaluated the hemodynamics of rapid administration of DDAVP into the isolated hindlimb in live rats and assessed this response after pretreatment with various antagonists. Thirty male Sprague-Dawley rats (350-450 g) were given intraperitoneal pentobarbital anesthesia (50 mg/kg). Perfusion was set at a rate that gave a control mean hindlimb perfusion pressure (HPP) of 100-120 mm Hg. Rats were assigned to five groups (N = 5, each group), with each rat serving as its own control. As a control, saline solution (in volumes equivalent to those used for the antagonists) was injected into the hindlimb preparation before the agonist injections. Each group received both the clinical preparation of DDAVP (i.e., with preservative) and a laboratory preparation of DDAVP in doses of 0.3-3 ng. Group 1 was tested before and after injection of saline solution control; group 2, before and after propranolol (0.5 mg/kg); group 3, before and after meclofenamate (1.5 mg/kg), a cyclooxygenase inhibitor; group 4, before and after nitroarginine (5 mg/kg) an inhibitor of nitric oxide synthesis; and group 5, before and after atropine sulfate (1 mg/kg). Chlorobutanol (25-75 micrograms), the preservative in the clinical preparation of DDAVP, was tested for changes in HPP in five rats similarly prepared. Systemic mean arterial pressure remained constant during the study. The HPP decreased with increasing doses of the clinical preparation of DDAVP, compared with saline solution controls, whereas no change occurred with the laboratory preparation of DDAVP.(ABSTRACT TRUNCATED AT 250 WORDS)
Jahr
J S
JS
Department of Anesthesiology, Tulane University School of Medicine, New Orleans, LA 70112.
Holton
R H
RH
Feng
C J
CJ
D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002724:Chlorobutanol / Q000494:pharmacology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects
D019335:Nitroarginine; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D001285:Atropine; D001120:Arginine; D011433:Propranolol; D003894:Deamino Arginine Vasopressin; D002724:Chlorobutanol