Arginine8-vasopressin reduces spinal cord blood flow after spinal subarachnoid injection in rats.
Arginine8-vasopressin (AVP) causes hindlimb paralysis, loss of nociceptive responsiveness and increased arterial pressure after spinal subarachnoid injection in rats. In these experiments, the effects of paralytic intrathecal doses of AVP on rat brain and spinal cord blood flow, vascular resistance and cardiac output were measured using radiolabeled microspheres. Ten minutes after injection, AVP (10-100 pmol) elevated mean arterial pressures significantly, increased vascular resistances in thoracic and lumbosacral spinal cord and reduced blood flow to the lumbosacral spinal cord without altering cardiac output, total peripheral resistance and blood flow to brain and other spinal cord regions. Lumbosacral blood flows remained significantly reduced 30 min after injection of 100 pmol of AVP, and recovered to pretreatment base-line levels by 60 min postinjection. Lactic acid concentrations were elevated significantly in spinal cerebrospinal fluid samples removed 5 to 15 min after AVP injection (100 pmol). The selective AVP V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] arg8-vasopressin, which previously blocked the effects of AVP on hindlimb motor and nociceptive function, in these experiments also blocked the AVP-induced increases in arterial pressure and reductions in lumbosacral perfusion. Intravenous infusion of the vasodilators papaverine and nifedipine failed to block AVP-induced hindlimb paralysis. Nifedipine, however, did accelerate subsequent recovery of hindlimb motor function, although it did not alter the lumbosacral blood flow reductions measured at 10 and 30 min after AVP injection. These findings indicate that AVP has significant vascular effects in the rat spinal cord that are associated with ischemia and neurological dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
Long
J B
JB
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, District of Columbia.
Martinez-Arizala
A
A
Johnson
S H
SH
Holaday
J W
JW
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects; D017483:Receptors, Vasopressin; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D010208:Papaverine; D009543:Nifedipine