Mechanism of pressor response to posterior hypothalamic injection of neuropeptide Y.
Unilateral microinjection of neuropeptide Y (NPY) into the posterior hypothalamic nucleus was previously found to evoke an increase in mean arterial pressure (MAP) in urethan-anesthetized rats. In this study, the mechanism by which this increase occurs was examined. Pretreatment of rats with 2.0 mg/kg (iv) of phenoxybenzamine, or 7.5 mg/kg (iv) of pentolinium, resulted in a significant reduction in the peak MAP evoked by microinjection of NPY (2.35 nmol) into the posterior hypothalamic nucleus. Administration of the vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)]AVP (10 micrograms/kg iv) before microinjection of NPY failed to attenuate the increase in MAP. Similar results were obtained with respect to the effect of these three antagonists on the increase in MAP evoked by injection of the cholinergic muscarinic agonist carbachol (5.48 nmol) into the posterior hypothalamic nucleus. Furthermore, microinjection of NPY or carbachol elicited a significant elevation of renal sympathetic nerve activity and an increase in resistance of the hindquarter vascular bed. However, NPY elicited a decrease and carbachol an increase in the resistance of the mesenteric bed, whereas NPY elicited an increase and carbachol a decrease in the resistance of the renal bed. These results suggest that NPY elicits an increase in MAP via centrally mediated sympathetic excitation. Furthermore, NPY and carbachol differentially affect sympathetic outflow to peripheral vascular beds after microinjection into the posterior hypothalamic nucleus.
Department of Pharmacology, St. Louis University School of Medicine, Missouri 63104.
J R
JR
Martin
M M
MM
Knuepfer
M C
MC
Beinfeld
T C
TC
Westfall
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001696:Biomechanical Phenomena; D001794:Blood Pressure / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D007034:Hypothalamus, Posterior; D007267:Injections; D007668:Kidney / Q000294:innervation; D009478:Neuropeptide Y / Q000494:pharmacology*; D010425:Pentolinium Tartrate / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D014667:Vasopressins / Q000037:antagonists & inhibitors
D009478:Neuropeptide Y; D010643:Phenoxybenzamine; D014667:Vasopressins; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D002217:Carbachol; D010425:Pentolinium Tartrate