Increased vasopressor actions of intraventricular neuropeptide Y-(13-36) in spontaneously hypertensive versus normotensive Wistar-Kyoto rats. Possible relationship to increases in Y2 receptor binding in the nucleus tractus solitarius.

Abstract

The C-terminal NPY fragment (13-36)[NPY-(13-36)], a Y2 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 (SHR). NPY-(13-36) was injected intracerebro-ventricularly in different doses (7.5 to 3000 pmol) in awake, unrestrained rats to evaluate the cardiovascular effects. NPY receptor subtypes were studied by autoradiography using [125I]peptide YY ([125I]PYY) as a radioligand and by masking the NPY Y1 and Y2 receptor subtypes with unlabelled [Leu31,Pro43]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 [125I]PYY binding in the nTS was 25% higher in SHR than in WKY rats. By masking the Y1 and Y2 receptor subtypes respectively it could be shown that this difference was due to an increase in Y2 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 pressor response in the SHR associated with a longer duration as compared with the WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)