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
Ja. Aguirre et al., 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, Brain research, 684(2), 1995, pp. 159-164
The C-terminal NPY fragment (13-36) [NPY-(13-36)], a Y-2 receptor agon
ist, elicits vasopressor responses upon central administration. The ca
rdiovascular responses of NPY-(13-36) together with the distribution o
f NPY receptor subtypes within the nucleus tractus solitarius (nTS) ha
ve therefore been studied in spontaneously hypertensive rats (SAR). NP
Y-(13-36) was injected intracerebro-ventricularly in different doses (
75 to 3000 pmol) in awake, unrestrained rats to evaluate the cardiovas
cular effects. NPY receptor subtypes were studied by autoradiography u
sing [I-125]peptide YY ([I-125]PPY) as a radioligand and by masking th
e NPY Y-1 and Y-2 receptor subtypes with unlabelled [Leu(31),Pro(43)]N
py 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 th
an in WKY rats. By masking the Y-1 and Y-2 receptor subtypes respectiv
ely 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 dur
ation as compared with the WKY rats. These enhanced vasopressor effect
s may partly be explained on the basis of an increased density of Y-2
receptor (vasopressor effects) vs. Y-1 receptor subtypes (vasodepresso
r 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.