neuropeptide-y and methylatropine

Injection of neuropeptide Y (NPY) into the hypothalamic paraventricular nucleus (PVN) inhibits gastric acid secretion in anesthetized rats. The role of the autonomic nervous system in mediation of this response was investigated. Unilateral microinjection of 200 pmol NPY into the PVN of anesthetized rats inhibited spontaneous and pentagastrin-stimulated gastric acid output. Inhibition was abolished by subdiaphragmatic vagotomy, atropine, and bethanechol but was restored by electrical stimulation of the distal cut end of the vagus in cervically vagotomized rats. Although sympathectomy, phenoxybenzamine, and yohimbine abolished the inhibition, it was not affected by prazosin treatment. Gastric blood flow was not altered by injection of NPY. These results suggest that the antisecretory effect of NPY in the PVN was sympathetically mediated via suppression of gastric vagal cholinergic tone through activation of alpha 2-adrenoceptors.

Topics: Animals; Atropine Derivatives; Autonomic Nervous System; Bethanechol; Bethanechol Compounds; Electric Stimulation; Gastric Acid; Male; Microinjections; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Pentagastrin; Rats; Rats, Sprague-Dawley; Vagotomy

The cardiovascular actions of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY) were examined in conscious, unrestrained rats. A prolonged decrease in heart rate (HR) and a fall in mean arterial pressure (MAP) were obtained following i.c.v. administration of NPY (1 and 10 micrograms). Passive immunization with an antiserum directed against NPY confirmed that the slowing of HR following i.c.v. administration of NPY was mediated via a central nervous mechanism and not from leakage of NPY out of the brain. Administration of NPY into different brain parenchymal regions identified a putative site of action in the rostral region of the solitary tract. The mechanism of the decrease in HR caused by centrally administered NPY was investigated by i.c.v. administration of NPY to animals that were pretreated with agents that altered autonomic tone. Administration of NPY to atropine-treated animals produced a reversal of the atropine-induced tachycardia, suggesting that the NPY-induced decrease in HR was not due to augmented vagal tone. However, administration of NPY to animals pretreated with propranolol did not significantly lower HR below that obtained with propranolol alone. These data suggest that i.c.v. administration of NPY may cause a decrease in cardiac sympathetic outflow. The effects of centrally administered NPY on baroreflex function were studied. The changes in HR caused by NPY did not significantly alter baroreflex set-point or gain. These studies provide evidence that NPY acted within a brainstem region to decrease sympathetic nervous outflow, resulting in a decrease in HR and MAP.

Topics: Animals; Atropine Derivatives; Blood Pressure; Catecholamines; Heart Rate; Male; Neuropeptide Y; Propranolol; Rats; Rats, Inbred Strains

The cardiovascular effects of intracisternal and intraparenchymal injection of neuropeptide Y (NPY) into the caudal ventrolateral medulla (CVLM) were investigated in anaesthetized normotensive rats. Intracisternal administration of 1.25 nmol NPY gave rise to a significant fall in blood pressure and heart rate, maximal 1 h postinjection. More localized microinjections of NPY into the CVLM similarly produced dose-dependent falls in blood pressure and heart rate. The bradycardia was significantly reduced or abolished by cardiac vagal blockade induced by: (1) pretreatment with the peripheral muscarinic antagonist methylatropine; or (2) ipsilateral vagotomy. These procedures also gave rise to a small reduction in the hypotensive response to NPY but the remaining component of the response was still significantly different from control, saline responses which were without significant haemodynamic effects. The results of this study provide further evidence for a central role for NPY in cardiovascular control. In the CVLM NPY responses appear to involve at least two different mechanisms: the fall in heart rate results from activation of cardiac vagal neurons in the nucleus ambiguus. The hypotensive response is more complex. The fall in blood pressure may be due in part to an activation of A1 noradrenergic neurons resulting in reduced sympathetic outflow but a small component of the response is a result of the profound slowing of the heart.

Topics: Animals; Atropine Derivatives; Blood Pressure; Cardiovascular System; Dose-Response Relationship, Drug; Heart Rate; Male; Medulla Oblongata; Microinjections; Neuropeptide Y; Rats; Rats, Inbred Strains; Vagus Nerve

Neuropeptide Y (NPY) is contained in and coreleased with norepinephrine (NE) from sympathetic nerves innervating vascular and cardiac tissues. The effects of NPY infusion on systemic hemodynamics and cardiac performance were compared with those of NE in conscious and pentobarbital sodium-anesthetized rats. A 10-min infusion of NPY (2 nmol.kg-1.min-1) decreased cardiac index (CI) 20% and stroke volume index (SVI) 9% with increases of 20% in mean arterial pressure (MAP) and 48% in total peripheral resistance (TPR). Conversely, NE (1.0 microgram.kg-1.min-1) increased SVI 14%, MAP 29%, and TRP 26%, with no change in CI. Heart rates decreased similarly (approximately 60 beats/min) but only NE-induced bradycardia was reversible by methylatropine nitrate. In anesthetized rats NPY (0.1 nmol.kg-1.min-1) increased left ventricular end-diastolic pressure (LVEDP) 20 +/- 10 mmHg (means +/- SD, n = 7) and decreased dP/dt by 8 +/- 6%. NE (0.07 microgram.kg-1.min-1) produced an equivalent pressor response, however, dP/dt rose 22 +/- 10% whereas LVEDP increased significantly less than with NPY. Thus NPY is a potent vasoconstrictor exerting similar effects to NE on MAP and TPR but, unlike NE, possesses negative inotropic and chronotropic activity.

Topics: Animals; Atropine Derivatives; Blood Pressure; Bradycardia; Depression, Chemical; Heart Rate; Hemodynamics; Male; Neuropeptide Y; Norepinephrine; Rats; Rats, Inbred Strains; Vasoconstriction