title: Evidence of systemic neuropeptide Y release after carbachol administration into the posterior hypothalamic nucleus.
abstract: The unilateral microinjection of the cholinergic agonist carbachol (CCh) directly into the posterior hypothalamic nucleus (PHN) of conscious rats evokes a dose-dependent increase in mean arterial pressure (MAP). Blockade of peripheral alpha-adrenoceptors and V1-vasopressin receptors completely inhibits this response, suggesting that the increase in MAP is mediated by increases in sympathoadrenal excitation and circulating vasopressin. Combining beta-adrenoceptor blockade with alpha-adrenoceptor and V1-vasopressin receptor blockade results in the return of a pressor response. To determine if neuropeptide Y (NPY) might be responsible for this increase, the putative NPY and irreversible alpha 1-adrenoceptor antagonist benextramine was added to alpha 2- and beta-adrenoceptor and V1-vasopressin receptor blockade provided by yohimbine, propranolol, and [D(CH2)5-Tyr(Me)]AVP (AVPX), respectively. Benextramine noncompetitively inhibited the pressor response to intravenous injection of NPY and the increase in MAP evoked by CCh microinjection into adrenergic and V1-vasopressin receptor-blocked rats, whereas benextramine competitively inhibited the pressor response to angiotensin II (AII). Furthermore, the combination of losartan, the selective AT1-AII receptor antagonist that completely blocked the increase in MAP evoked by intravenous AII, and adrenergic and V1-vasopressin receptor antagonists did not attenuate the pressor response evoked by CCh microinjection into the PHN or the increase in MAP evoked by intravenous injection of NPY. These results indicate that AII was not responsible for the CCh-evoked increase in MAP in the presence of adrenergic and V1-vasopressin receptor blockade. The similarity in the antagonism of the increase in MAP evoked by intravenous NPY injection and by CCh microinjection into the PHN of adrenergic- and V1-vasopressin receptor-blocked rats suggests that NPY might be released from sympathetic neurons after activation of the sympathetic nervous system by central administration of CCh into the PHN.
authors.affiliation: Department of Pharmacology, Kirksville College of Osteopathic Medicine, MO 63501, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Martin
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007034:Hypothalamus, Posterior / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular; D009478:Neuropeptide Y / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D009478:Neuropeptide Y; D010277:Parasympathomimetics; D015016:Yohimbine; D002217:Carbachol