Neuropeptides in hypertension: role of neuropeptide Y and calcitonin gene related peptide.
1. The effect of neuropeptide Y (NPY) on cardiovascular function at three levels of the noradrenergic axis where the peptide is known to co-exist with noradrenaline (NA) and or adrenaline (A) was studied in normotensive Sprague-Dawley (SD), Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). 2. In the perfused mesenteric arterial bed, NPY and the structurally similar peptide intestinal polypeptide (PYY) decreased the periarterial nerve stimulation induced release of NA and potentiated the increase in perfusion pressure to nerve stimulation or exogenously applied agonists (e.g. angiotensin, vasopressin, phenylephrine). In contrast to NPY and PYY, C-terminal NPY fragments inhibited NA release and produced a parallel decrease in perfusion pressure thus supporting the concept of Y1 (post) and Y2 (pre) NPY receptors. 3. In the mesenteric artery of SHR the prejunctional inhibitory effect of NPY was attenuated while the postjunctional response was enhanced. 4. Following intrathecal (Int) injection of NPY, there was a decrease in blood pressure, total peripheral resistance (predominantly by a decrease in mesenteric vascular resistance) and renal nerve activity. The depressor effect of Int NPY was attenuated in the SHR. 5. Unilateral injections of NPY into the posterior hypothalamic nucleus increased blood pressure, hindquarter and renal vascular resistance and renal nerve activity. The pressor effect was enhanced in the SHR. 6. Periarterial nerve stimulation of the perfused mesenteric artery produced a frequency dependent vasodilation in beds pretreated with guanethidine and precontracted with methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Westfall
T C
TC
Department of Pharmacology, St Louis University Medical Center, MO 63104.
Han
S P
SP
Knuepfer
M
M
Martin
J
J
Chen
X L
XL
del Valle
K
K
Ciarleglio
A
A
Naes
L
L
D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D004837:Epinephrine / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007278:Injections, Spinal; D008297:Male; D008845:Microinjections; D009451:Neuroeffector Junction / Q000187:drug effects; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013152:Splanchnic Circulation / Q000187:drug effects
D009478:Neuropeptide Y; D015740:Calcitonin Gene-Related Peptide; D009638:Norepinephrine; D004837:Epinephrine