[Tyr1]-nociceptin has naloxone-insensitive vasodilator activity in the hindquarters vascular bed of the rat.

The heptadecapeptide nociceptin, also known as Orphanin FQ, is a newly-discovered endogenous ligand for the opioid-like G-protein-coupled receptor ORL1. In the present study, in order to investigate the structure-activity relationship for nociceptin, responses to nociceptin, [Tyr1]-nociceptin, nociceptin-(2-17), nociceptin-(1-11), and nociceptin-(1-7) were compared in the hindquarters vascular bed of the rat. Injections of nociceptin (1-30 nmol), [Tyr1]-nociceptin (1-30 nmol), and met-enkephalin (10-300 nmol) induced dose-related decreases in hindquarters perfusion pressure, whereas injections of similar volumes of the saline vehicle had no effect.

Decreases in systemic arterial and hindquarters perfusion pressure in response to nociceptin are not inhibited by naloxone in the rat.

Nociceptin, the endogenous ligand for the ORL1 receptor, has been shown to decrease systemic arterial and hindquarters perfusion pressures in the rat. The present study was undertaken to determine if decreases in systemic arterial and hindquarters perfusion pressures, in response to nociceptin, are mediated by a naloxone-sensitive mechanism. Injections of nociceptin decreased systemic arterial and hindquarters perfusion pressures in a dose-related manner.

Endomorphin 1 and 2, endogenous ligands for the mu-opioid receptor, decrease cardiac output, and total peripheral resistance in the rat.

Endomorphin 1 and 2 are recently discovered endogenous ligands for the mu-opioid receptor. In the present study, responses to intravenous administration of endomorphin 1 and 2 were investigated in the systemic vascular bed of the rat. Endomorphin 1 and 2 induced dose-related decreases in systemic arterial pressure when injected in doses of 10-100 nmol/kg i.

Comparison of responses to T-kinin and bradykinin in the mesenteric vascular bed of the cat.

Responses to T-kinin and bradykinin were compared in the mesenteric vascular bed of the cat. Under constant-flow conditions, injection of T-kinin and bradykinin into the perfusion circuit induced similar dose-related decreases in perfusion pressure. Responses to T-kinin and bradykinin were inhibited by the kinin B2 receptor antagonist Hoe-140, but were not altered by the B1 receptor antagonist des-Arg9-[Leu8]-BK, the histamine H1 antagonist pyrilamine, the histamine H2 receptor antagonist cimetidine, or the H3 receptor antagonist thioperamide.

Nociceptin, an endogenous ligand for the ORL1 receptor, has vasodilator activity in the hindquarters vascular bed of the rat.

The heptadecapeptide nociceptin, also known as Orphanin FQ, is a newly discovered endogenous ligand for the G-protein coupled, opioid-like receptor ORL1. In the present study, responses to intra-arterial injections of nociceptin were investigated in the hindquarters vascular bed of the rat. Under constant-flow conditions nociceptin induced dose-dependent decreases in hindquarters perfusion pressure when injected in doses of 1-30 nmol into the hindquarters perfusion circuit.

Nociceptin, an endogenous ligand for the ORL1 receptor, decreases cardiac output and total peripheral resistance in the rat.

The heptadecapeptide nociceptin, also known as Orphanin FQ, is a newly discovered endogenous ligand for the opioid-like G-protein coupled receptor, ORL1. In the present study, responses to intravenous injections of nociceptin were investigated in the systemic vascular bed of the rat. Nociceptin induced dose-related decreases in systemic arterial pressure and total peripheral resistance when injected in doses of 1-30 nmol/kg i.

Tone-dependent vasodilator responses to proadrenomedullin NH2-terminal 20 peptide in the hindquarters vascular bed of the rat.

Responses to proadrenomedullin NH2-terminal 20 peptide (PAMP) were investigated in the systemic and hindquarters vascular bed of the rat. Intravenous injections of PAMP and adrenomedullin (ADM) produced dose-related decreases in systemic arterial and hindquarters perfusion pressure, which were not altered by alpha-receptor or adrenergic nerve terminal blocking agents. PAMP was 100-fold less potent than ADM, and hindquarters vasodilator responses to both peptides were similar in innervated and denervated preparations.

Effects of captopril on responses to bradykinin in the hindquarters vascular bed of the rat.

The effects of captopril, and angiotensin converting enzyme (ACE) inhibitor, on responses to bradykinin (BK), to angiotensin (Ang) I and II, and to other agonists were investigated in the hindquarters vascular bed of the rat. Under conditions of controlled flow, intra-arterial (i.a.

Adrenomedullin (16-31) has pressor activity in the rat but not the cat.

Responses to a newly synthesized human adrenomedullin (hADM) analog, hADM (16-31), were investigated in the rat and cat. Unlike the full-sequence peptide, which has potent hypotensive activity, hADM (16-31) had pressor activity in the rat but not in the cat. Injection of hADM (16-31) in doses of 10-300 nmol/kg i.

Nociceptin, an endogenous ligand for the ORL1 receptor, has novel hypotensive activity in the rat.

The heptadecapeptide nociceptin, also known as Orphanin FQ, is a newly discovered endogenous ligand for the opioid-like G-protein coupled receptor, ORL1. In the present study responses to intravenous administration of nociceptin were investigated in the systemic vascular bed of the rat. Nociceptin induced dose-related decreases in systemic arterial pressure when injected in doses of 1-30 nmol/kg i.

Proadrenomedullin NH2-terminal peptide (PAMP)(12-20) has vasodepressor activity in the rat and cat.

Decreases in systemic arterial pressure in response to human proadrenomedullin NH2-terminal 20 peptide (hPAMP), a truncated analog, hPAMP(12-20), and human adrenomedullin (hADM) were compared in the rat and cat. The order of potency was hADM > hPAMP > hPAMP(12-20). hPAMP(12-20) was approximately 3-fold less potent than the full sequence peptide, hPAMP, and 10-fold less potent than the related peptide, hADM.

Adrenomedullin-(22-52) antagonizes vasodilator responses to CGRP but not adrenomedullin in the cat.

The effects of adrenomedullin (ADM)-(22-52), a putative ADM receptor antagonist, on vasodilator responses to ADM and the structurally related peptide, calcitonin gene-related peptide (CGRP), were investigated in the hindlimb vascular bed of the cat under constant-flow conditions. ADM-(22-52) had no significant effect on hindlimb perfusion pressure when injected in doses up to 120 nmol; after administration of ADM-(22-52), vasodilator responses to ADM were unchanged, whereas vasodilator responses to CGRP were inhibited. The inhibitory effects of ADM-(22-52) on responses to CGRP were selective and reversible and were similar to the inhibitory effects of the CGRP antagonist CGRP-(8-37).

Analysis of cardiovascular responses to PACAP-27, PACAP-38, and vasoactive intestinal polypeptide.

Responses to pituitary adenylate cyclase polypeptide (PACAP)-27, PACAP-38, and vasoactive intestinal peptide (VIP) were compared in the peripheral and pulmonary vascular beds of the cat and in the isolated perfused neonatal pig heart. Intravenous injections of PACAP-27 and PACAP-38 produced biphasic changes in systemic arterial pressure whereas iv injections of VIP caused only decreases in arterial pressure. When blood flow to the hind limb and mesenteric vascular beds was maintained constant, PACAP-27 and PACAP-38 caused dose-related biphasic changes in perfusion pressure, whereas VIP only decreased perfusion pressure.

Catecholamine release mediates pressor effects of adrenomedullin-(15-22) in the rat.

Human adrenomedullin, a novel hypotensive peptide, contains a six-member ring structure similar to that found in calcitonin gene-related peptide and pancreatic amylin. Unlike the full-sequence peptide, human adrenomedullin-(15-22) [hADM-(15-22)], which contains the ring structure, increases systemic arterial pressure in the rat but not the cat. We undertook the present study to investigate the mechanism by which hADM-(15-22) increases systemic arterial pressure in the rat.

Analysis of responses to angiotensin I and angiotensin I-(3-10) in the mesenteric vascular bed of the cat.

Responses to angiotensin I and antiogensin I-(3-10), the precursors for angiotensin II and IV, were investigated in the mesenteric vascular bed of the cat. Under constant-flow conditions, injections of precursors and the active peptides into the mesenteric arterial perfusion circuit caused dose-related increases in receptor antagonist that were attenuated by the angiotensin AT1 receptor antagonist DuP532 (2-propyl-4-pentafluorethyl-1-[2'-(2H-tetrazol-5-YL)-1,1'-bi phenyl-4-YL methyl]1H-imidazole-5-carboxylic acid), but not by the angiotensin AT2 receptor antagonist PD123,319 ((S)1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl )-4,5,6,7- tetrahydro-1H-imadazo[4,5-c]pyridine-6-carboxylic acid, ditriflouroacetate]). Responses to angiotensin I and II were similar as were responses to angiotensin I-(3-10) and angiotensin IV, and these responses were not altered by the presence of a time-delay coil in the perfusion circuit.

Inhibitory Effects of LY301875 on Responses to Angiotensin Peptides in Pulmonary Vascular Bed of the Cat.

The effects of the nonpeptide angiotensin receptor antagonist LY301875 on responses to angiotensin II, angiotensin III, and angiotensin IV were investigated in the pulmonary vascular bed of the intact cat chest. Under conditions of controlled blood flow, injections of the angiotensin peptides into the perfused lobar artery caused dose-related increases in lobar arterial pressure, and LY301875 decreased pressor responses to angiotensin II, angiotensin III, and angiotensin IV. The duration of the blockade was related to the dose of the antagonist, and LY301875 had no significant effect on pressor responses to U-46619, norepinephrine, serotonin or BAY K 8644.

Influence of HOE 140, A Bradykinin Receptor Antagonist, in the Isolated Mesenteric Vascular Bed of the Rat.

The inhibitory effects of HOE 140 (D-Arg-[Hyp(3),Thi(5),D-Tic(7), Oic(8)]bradykinin), a novel bradykinin B(2)-receptor antagonist, on mesenteric vascular bed vasodilator responses to bradykinin (BK) were investigated under constant-flow conditions in the isolated blood-perfused rat mesenteric vascular bed. During baseline conditions, injections of BK produced dose-related decreases in mesenteric arterial perfusion pressure which were reproducible with respect to time. HOE 140, in a dose of 50 &mgr;g/kg intravenously, decreased vasodilator responses to BK but had no significant effect on mesenteric vasodilator responses to albuterol, acetylcholine, levcromakalim, or to nitroglycerin.

Pulmonary vasodilator responses to adrenomedullin are reduced by NOS inhibitors in rats but not in cats.

Responses to and the mechanism of action of adrenomedullin (ADM), the carboxy-terminal fragments of ADM, and calcitonin gene-related peptide (CGRP), a structurally related peptide, were investigated in the pulmonary vascular bed of the rat. Under conditions of elevated tone and controlled pulmonary blood flow in the isolated blood-perfused rat lung, injections of ADM, the 15-52 amino acid carboxy-terminal ADM analogue (ADM15-52), and CGRP caused dose-related decreases in pulmonary arterial perfusion pressure. In contrast, the carboxy-terminal 22-52 and 40-52 amino acid fragments had no consistent vasodilator activity.

Comparative Effects of N(omega)-L-Nitro-L-Arginine Methyl Ester and N(omega)-L-Nitro-L-Arginine Benzyl Ester in the Mesenteric Circulation of the Rat.

Comparative effects of the nitric oxide (NO) synthase inhibitors, N(omega)-L-nitro-L-arginine methyl ester, and N(omega)-L-nitro-L-arginine benzyl ester on baseline arterial tone and on vasodilator responses to acetylcholine, isoproterenol, prostaglandin E(1), histamine, and nitroglycerin were investigated in the isolated mesenteric vascular bed of the rat. Under constant-flow conditions, intra-arterial (IA) injections of acetylcholine (100 ng--1 &mgr;g), isoproterenol (100 ng--1 &mgr;g), prostaglandin E(1) (0.3--3 &mgr;g), histamine (300 ng--3 &mgr;g), and nitroglycerin (100 ng--1 &mgr;g) caused dose-related decreases in mesenteric arterial perfusion pressure and decreases in systemic arterial pressure.

Analysis of responses to angiotensin I-(3-10) in the hindlimb vascular bed of the cat.

Responses to angiotensin I-(3-10), the precursor for angiotensin IV, were investigated in the anesthetized cat. Intravenous injections of the precursor caused dose-related increases in systemic arterial pressure that were similar to responses elicited by angiotensin i.v.

Effects of zaprinast and dissolved nitric oxide on the pulmonary circulation of fetal sheep.

This study was designed to determine indirectly if the changes in ovine fetal pulmonary vascular tone caused by i.v. injections of nitric oxide-containing solutions are mediated by cGMP.

Contractile and coronary vascular effects of pituitary adenylate cyclase activating polypeptide in neonatal pig hearts.

Objective: The purpose was to investigate the influence of the 38-amino-acid neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP38), on contractile function and coronary vascular tone in neonatal hearts.

Methods: Isolated, paced (150 bpm), isovolumically-beating, piglet hearts (n = 19) underwent retrograde aortic perfusion at constant coronary flow (approximately 2.5 ml/min/gwet) with an erythrocyte-enriched (Hct 15-20%) solution (37 degrees C).

Analysis of responses to pentoxifylline in the pulmonary vascular bed of the cat.

Objective: To test the hypothesis that pulmonary vasodilator responses to pentoxifylline are dependent on the synthesis of nitric oxide from L-arginine and are independent of the release of cyclooxygenase products.

Design: Prospective study.

Setting: Research laboratory.

Proadrenomedullin NH2-terminal 20 peptide has cAMP-mediated vasodilator activity in the mesenteric vascular bed of the cat.

Responses to proadrenomedullin NH2-terminal 20 peptide (hPAMP), a truncated analogue [hPAMP(12-20)], and adrenomedullin (hADM) were investigated in the mesenteric vascular bed of the cat. Under constant-flow conditions, injections of hPAMP, hPAMP(12-20), and hADM caused dose-related decreases in mesenteric perfusion pressure. hADM was 100-fold more potent than hPAMP, and 1000-fold more potent than hPAMP(12-20).