INCREASED VASOPRESSOR ACTIONS OF INTRAVENTRICULAR NEUROPEPTIDE Y-(13-36) IN SPONTANEOUSLY HYPERTENSIVE VERSUS NORMOTENSIVE WISTAR-KYOTO RATS - POSSIBLE RELATIONSHIP TO INCREASES IN Y-2 RECEPTOR-BINDING IN THE NUCLEUS-TRACTUS-SOLITARIUS

The C-terminal NPY fragment (13-36) [NPY-(13-36)], a Y-2 receptor agonist, elicits vasopressor responses upon central administration. The cardiovascular responses of NPY-(13-36) together with the distribution of NPY receptor subtypes within the nucleus tractus solitarius (nTS) have therefore been studied in spontaneously hypertensive rats (SAR). NPY-(13-36) was injected intracerebro-ventricularly in different doses (75 to 3000 pmol) in awake, unrestrained rats to evaluate the cardiovascular effects. NPY receptor subtypes were studied by autoradiography using [I-125]peptide YY ([I-125]PPY) as a radioligand and by masking the NPY Y-1 and Y-2 receptor subtypes with unlabelled [Leu(31),Pro(43)]Npy and NPY-(13-36) respectively. In both male SHR and age-matched male normotensive Wistar-Kyoto rats (WKY) NPY-(13-36) injections elicited vasopressor effects. In WKY this effect was dose-dependent and became significant at doses from 75 pmol, whereas in the SHR the vasopressor effect had a longer duration than in the WKY and became significant at lower doses (25 pmol) but associated with the development of an early ceiling effect. The heart rate was unaffected in both groups of rats. Total specific [I-125]PYY binding in the nTS was 25% higher in SHR than in WKY rats. By masking the Y-1 and Y-2 receptor subtypes respectively it could be shown that this difference was due to an increase in Y-2 receptor binding within the nTS. The present results give evidence for an increased potency but not an increased efficacy of NPY-(13-36) in inducing a presser response in the SHR associated with a longer duration as compared with the WKY rats. These enhanced vasopressor effects may partly be explained on the basis of an increased density of Y-2 receptor (vasopressor effects) vs. Y-1 receptor subtypes (vasodepressor effects) leading to a dominance of Y-2 over Y-1 transduction in the SHR. The peak activity of NPY-(13-36) in SHR may not be increased due to the already high blood pressure levels in these rats.