Hindlimb paralytic effects of arginine vasopressin and related peptides following spinal subarachnoid injection in the rat.
Intrathecal (IT) injection of arginine vasopressin (AVP) in rats caused a transient (less than 30 min), dose-related paralysis of the hindlimbs, loss of hindlimb and tail nociceptive responsiveness, and increased mean arterial pressure. Motor dysfunction was produced with comparable potency by lysine vasopressin (LVP) and arginine vasotocin (AVT); oxytocin (OXY) was approximately 1000 times less potent. Paralysis induced by these peptides was selectively blocked following IT pretreatment with 0.5 nmoles of the vasopressin V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] Arg8-vasopressin (d(CH2)5[Tyr(Me2)]AVP). Pressor and antinociceptive responses to AVP were also blocked by this compound. However, at higher doses (2-5 nmoles, IT), d(CH2)5[Tyr(Me2)]AVP produced hindlimb paralysis, antinociception, and pressor responses by itself. In contrast to the fiber degeneration, cell loss, and necrosis found in lumbosacral cords of rats persistently paralyzed by other peptides (dynorphin A, somatostatin, and ICI 174864), neuropathological changes were not evident in spinal cords of rats transiently paralyzed by IT AVP. These results indicate that AVP-related peptides affected diverse spinal cord functions through interactions with a V1-like receptor. The similar pattern of cardiovascular and antinociceptive responses to other peptides (dynorphin A, somatostatin, and ICI 174864), which also caused hindlimb paralysis, suggests that the former responses may actually reflect the nonselective consequences of a peptide-induced disruption of spinal cord function, rather than specific shared pharmacological effects.
Long
J B
JB
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Martinez-Arizala
A
A
Rigamonti
D D
DD
Holaday
J W
JW
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D006614:Hindlimb; D007278:Injections, Spinal; D008236:Lypressin / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology; D010243:Paralysis / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D013346:Subarachnoid Space; D014668:Vasotocin / Q000494:pharmacology
D001127:Arginine Vasopressin; D010121:Oxytocin; D008236:Lypressin; D014668:Vasotocin