Regional haemodynamic responses to pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide in conscious rats.
1. Regional haemodynamic responses to the homologous peptides, pituitary adenylate cyclase-activating peptide (1-27) (PACAP27) and vasoactive intestinal polypeptide (VIP) were assessed by giving 20 min infusions (1.5-15 nmol kg-1 h-1) in conscious, chronically-instrumented, Long Evans rats. 2. PACAP27 caused dose-dependent depressor and tachycardic effects associated with renal, mesenteric and hindquarters vasodilatations, although only in the latter vascular bed was there a sustained increase in flow. 3. VIP caused dose-dependent depressor and tachycardic effects that were not significantly different from those caused by equimolar doses of PACAP27. However, the hindquarters vasodilator effects of VIP (at 7.5 and 15 nmol kg-1 h-1) were greater than those of PACAP27 (at the same doses), and accompanied by reductions in renal and mesenteric flows and conductances. 4. In the presence of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 11 mumol kg-1 h-1), there was significant inhibition of the hindquarters vasodilator effects of PACAP27 and VIP (at 7.5 and 15 nmol kg-1 h-1). Under these circumstances the renal and mesenteric vasoconstrictor effects of VIP were abolished. 5. The beta 2-adrenoceptor antagonist, ICI 118551 (670 nmol kg-1 bolus, 335 nmol kg-1 h-1 infusion), reduced the matched hindquarters vasodilator responses to PACAP27 (15 nmol kg-1 h-1) and VIP (7.5 nmol kg-1 h-1), and also abolished the renal vasoconstrictor effects of VIP. 6. The AT1-receptor antagonist, losartan potassium (20 mumol kg-1), had no significant effect on the haemodynamic response to PACAP27 (15 nmol kg-1 h-1), but augmented the hypotensive action of VIP (7.5 nmol kg-1 h-1). This influence of losartan was associated with conversion of the renal and mesenteric vasoconstrictor effect of VIP to vasodilatation. 7. Our findings show that similar changes in mean systemic arterial blood pressure in response to PACAP27 and VIP conceal substantial differences in their regional haemodynamic actions. Although the hindquarters vasodilator effects of both peptides involve NO- and Beta2-adrenoceptor-mediated mechanisms,it appears that activation of the renin-angiotensin system contributes significantly to the haemodynamic effects of VIP, but not to those of PACAP27.
Gardiner
S M
SM
Department of Physiology & Pharmacology, University of Nottingham Medical School, Queen's Medical Centre.
Rakhit
T
T
Kemp
P A
PA
March
J E
JE
Bennett
T
T
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007262:Infusions, Intravenous; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009479:Neuropeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*
C495403:Adcyap1 protein, rat; D000319:Adrenergic beta-Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011412:Propanolamines; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D012965:Sodium Chloride; C026777:ICI 118551; D001120:Arginine; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester