RESUMEN
IV bolus administration of 2.5-50 micrograms NPY (0.6-12.5 nmol) to conscious rats produced a dose- and time-dependent increase in systolic and diastolic blood pressure. Following priming with 2.5 micrograms NPY, or larger doses, the subsequent administrations of noradrenaline produced pressor responses that were potentiated both in magnitude and duration. The NPY-induced potentiation of the pressor response to noradrenaline was dose-dependent and extended to the pressor action of adrenaline and angiotensin II but not to the hypotensions produced by bradykinin or isoproterenol. The potentiation was not related to the fact that multiple doses of catecholamines were repeated. Reserpine did not substantially modify the NPY-induced potentiation of the pressor activity of the catecholamines. Chemical sympathectomy following 6-hydroxydopamine caused a marked supersensitivity to the catecholamines and NPY but obliterated the NPY-induced potentiation of the pressor effect of adrenaline. Nifedipine reduced the pressor action of the catecholamines and NPY but did not attenuate the NPY-induced potentiation of the pressor action of catecholamines. It is concluded that the acute pressor effect of NPY and of the potentiation of the catecholamine pressor effects involve different mechanisms.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Epinefrina/farmacología , Neuropéptido Y/farmacología , Norepinefrina/farmacología , Animales , Antihipertensivos/farmacología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Hexametonio , Compuestos de Hexametonio/farmacología , Hidroxidopaminas/farmacología , Masculino , Nifedipino/farmacología , Oxidopamina , Ratas , Ratas Endogámicas , Valores de Referencia , Reserpina/farmacologíaRESUMEN
The present study was performed to evaluate the effect of 3rdV injection on water intake of brain natriuretic peptide (BNP), which is structurally different from the atrial natriuretic peptide. BNP was recently isolated from porcine brain and appears to have a different precursor than the family of atrial natriuretic peptides. Central administration of BNP 3rdV decreased water intake. At a dose of 2.0 nmol/rat, BNP partially inhibited dehydration-induced water intake and completely blocked the stimulatory effect of 478 pmol/rat angiotensin II in rats.
Asunto(s)
Angiotensina II/farmacología , Deshidratación/complicaciones , Ingestión de Líquidos , Proteínas del Tejido Nervioso/administración & dosificación , Animales , Inyecciones Intraventriculares , Masculino , Péptido Natriurético Encefálico , Proteínas del Tejido Nervioso/farmacología , Ratas , Ratas EndogámicasRESUMEN
The role of neuropeptide tyrosine (NPY) on adrenergic neurotransmission was assessed in the rat vas deferens transmurally stimulated with square pulses of 0.15 or 15 Hz. Nanomoles of NPY inhibited the electrically-induced contractions on the prostatic half but not on the epididymal end of the ductus. NPY was at least 200-fold more potent than norepinephrine or adenosine to produce an equivalent inhibition. Complete amino acid sequence of NPY is required for full agonist activity; deletion of tyrosine at the amino terminus, i.e., NPY fragment 2-36 was 3-fold less potent than the native peptide. NPY fragment 5-36, 11-36 or 25-36 were proportionally less potent than NPY. Avian pancreatic polypeptide was inactive. The presynaptic nature of the NPY activity was established measuring the outflow of 3H-norepinephrine from the adrenergic varicosities of the vas deferens electrically stimulated. In this assay, NPY was more potent than NPY 2-36 or NPY fragment 5-36. No inhibitory action of NPY was detected in K+ depolarized tissues. The inhibitory effect of NPY on the rat vas deferens neurotransmission was not significantly modified by yohimbine, theophylline or naloxone, indicating that the effect of NPY is not due to the activation of alpha 2-adrenoceptors, adenosine receptors or opiate receptors respectively. Picrotoxin or apamin did not modify the inhibitory potency of NPY; verapamil or methoxyverapamil significantly reduced its potency. The inhibitory action of NPY is best explained through the activation of presynaptic NPY receptors that regulate norepinephrine release via a negative feedback mechanism. Structure activity studies give support to the notion of NPY receptors.