Analysis of systemic and pulmonary vascular responses to PACAP and VIP: role of adrenal catecholamines.
Systemic and pulmonary vascular responses to pituitary adenylate cyclase-activating polypeptide (PACAP), a novel peptide with 68% sequence homology to vasoactive intestinal peptide (VIP), were investigated in the anesthetized cat. Intravenous injections of PACAP in doses of 0.1-3.0 nmol/kg produced decreases in arterial pressure (AP) at low doses and biphasic changes (decreases followed by increases) at higher doses, which were accompanied by increases in central venous pressure (CVP) and cardiac output (CO), and decreases and biphasic changes in systemic vascular resistance (SVR). In contrast, VIP in doses of 0.1-3.0 nmol/kg produced only dose-dependent decreases in AP and SVR and produced little change in CVP and CO. PACAP produced increased pulmonary arterial pressure (PAP), left atrial pressure (LAP), and increases in pulmonary vascular resistance (PVR). PACAP increased heart rate (HR) and right ventricular contractile force (RVCF), while VIP had no effect. Increases in AP and SVR in response to PACAP were changed to decreases following the administration of phentolamine or after adrenalectomy. Under constant flow conditions, PACAP and VIP produced dose-dependent decreases in lobar arterial pressure when tone was elevated, with PACAP being threefold more potent than VIP. Meclofenamate and nitro-L-arginine methyl ester (L-NAME) had no effect on pulmonary responses to the peptides. PACAP produced dose-dependent biphasic changes in hindquarters perfusion pressure, whereas VIP produced only decreases that were unchanged by indomethacin, L-NAME, and glibenclamide. Phentolamine and adrenalectomy eliminated the hindquarters pressor response to PACAP and D-Phe2-VIP, a VIP antagonist, reduced responses to VIP but not to PACAP. These data suggest that responses to PACAP and VIP are mediated by distinct receptors and that pressor responses to PACAP are due to the release of catecholamines from the adrenal gland.
Minkes
R K
RK
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
McMahon
T J
TJ
Higuera
T R
TR
Murphy
W A
WA
Coy
D H
DH
Kadowitz
P J
PJ
D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002395:Catecholamines / Q000502:physiology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011652:Pulmonary Circulation / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D002395:Catecholamines; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D010646:Phentolamine