Qingzhong Hao

NOCICEPTIN : AN ENDOGENOUS AGONIST FOR CENTRAL OPIOID LIKE1 (ORL1) RECEPTORS POSSESSES SYSTEMIC VASORELAXANT PROPERTIES

The purpose of the present study was to investigate the effects of nociceptin on peripheral arterial rings from the cat. When feline renal, mesenteric, carotid and femoral rings with intact endothelium were precontracted with phenylephrine (100 nanomolar), nociceptin (3 x 10(-11)-3 x 10(-6) M) decreased tension in a concentration-dependent manner. The present data suggest nociceptin possesses biologic activity outside the CNS and may contribute to the regulation of systemic blood pressure and regional blood flow.

An adrenomedullin (ADM) fragment retains the systematic vasodilator activity of human ADM

The present study was undertaken to investigate the effects of human ADM, a newly discovered peptide present in normal human plasma, as well as a fragment of human ADM, human ADM13-52, on systemic hemodynamics in the anesthetized cat. Intravenous (i.v.) bolus injections of human ADM and human ADM13-52 decreased systemic arterial pressure (SAP) in a dose-dependent manner. Since neither peptide altered cardiac output, the decreases in SAP reflect reductions in systemic vascular resistance. The systemic vasodilator responses to the same doses of human ADM and human ADM13-52 in the cat were similar. The present study demonstrates the systemic vasodilator activity of ADM is conserved across species. The present data suggest that human ADM13-52 or a peptide structurally similar to it may mediate the hemodynamic properties of ADM in vivo in man. Since cardiac output and heart rate were not altered during the marked systemic vasodepressor response to ADM, activation of the ADM vasodilator mechanism may represent a therapeutic alternative in the clinical management of hypertensive diseases.

Novel catheterization technique for the in vivo measurement of pulmonary vascular responses in rats

A novel cardiac catheterization technique was devised to investigate the pulmonary arterial pressure-blood flow relationship in intact spontaneously breathing rats (ISBR) under physiological conditions with constant left atrial pressure and controlled blood flow within the normal range. Observations using this new technique in vivo were contrasted with data derived with isolated perfused rat lungs in vitro. Unlike results in in vitro isolated perfused rat lungs, the pressure-flow curves in vivo were curvilinear, with pulmonary artery pressure increasing more rapidly at low pulmonary blood flows of 4-8 ml/min and less rapidly at higher flow rates. Pressure-flow curves were reproducible and were not altered by 1-1.5 h of arrested perfusion, cyclooxygenase blockade, or perfusion with aortic or mixed venous blood. In contrast to results in in vitro isolated perfused rat lungs, NG-nitro-L-arginine methyl ester (L-NAME) increased pulmonary arterial pressure at all but the lowest flow rates with a slight effect on the curvilinear pressure-flow relationship. L-NAME reversed pulmonary vasodilator responses to acetylcholine and bradykinin and enhanced the pulmonary vasodilator response to nitroglycerin. The present data suggest that actively induced pulmonary hypertension is under greater control by endothelium-derived relaxing factor (EDRF). Unlike previous results in in vitro perfused rat lungs, results in ISBR demonstrate that the pulmonary vasodilator response to adrenomedullin-(13-52) is not mediated by calcitonin gene-related peptide receptors, which are not coupled to the release of EDRF. These results indicate that this novel technique may provide a useful model for the study of the pulmonary circulation in the intact chest rat.A novel cardiac catheterization technique was devised to investigate the pulmonary arterial pressure-blood flow relationship in intact spontaneously breathing rats (ISBR) under physiological conditions with constant left atrial pressure and controlled blood flow within the normal range. Observations using this new technique in vivo were contrasted with data derived with isolated perfused rat lungs in vitro. Unlike results in in vitro isolated perfused rat lungs, the pressure-flow curves in vivo were curvilinear, with pulmonary artery pressure increasing more rapidly at low pulmonary blood flows of 4-8 ml/min and less rapidly at higher flow rates. Pressure-flow curves were reproducible and were not altered by 1-1.5 h of arrested perfusion, cyclooxygenase blockade, or perfusion with aortic or mixed venous blood. In contrast to results in in vitro isolated perfused rat lungs, N G-nitro-l-arginine methyl ester (l-NAME) increased pulmonary arterial pressure at all but the lowest flow rates with a slight effect on the curvilinear pressure-flow relationship. l-NAME reversed pulmonary vasodilator responses to acetylcholine and bradykinin and enhanced the pulmonary vasodilator response to nitroglycerin. The present data suggest that actively induced pulmonary hypertension is under greater control by endothelium-derived relaxing factor (EDRF). Unlike previous results in in vitro perfused rat lungs, results in ISBR demonstrate that the pulmonary vasodilator response to adrenomedullin-(13-52) is not mediated by calcitonin gene-related peptide receptors, which are not coupled to the release of EDRF. These results indicate that this novel technique may provide a useful model for the study of the pulmonary circulation in the intact chest rat.

Agmatine: A novel endogenous vasodilator substance

The purpose of the study was to investigate the effects of agmatine, an endogenous clonidine-displacing substance (CDS), on systemic hemodynamics in the anesthetized rat. Bolus intravenous (i.v.) injections of agmatine decreased systemic arterial pressure (SAP) and systemic vascular resistance in a dose-dependent manner. The development of acute tachyphylaxis to the systemic vasodepressor response to agmatine did not induce cross-tachyphylaxis to the systemic vasodepressor responses to bradykinin, isoproterenol and nitroglycerin. The present data demonstrate agmatine, as a CDS and agonist for imidazoline (I) receptors, possesses marked systemic vasodilator activity in the rat. The present data suggest that activation of I receptors may represent a novel mechanism of vasodilation in vivo.

Adrenotensin: An adrenomedullin gene product contracts pulmonary blood vessels

The purpose of the present study was to determine the effects of adrenotensin, a newly described product of the ADM gene, on cat pulmonary arterial (PA) rings. Under resting conditions, adrenotensin increased tension of PA rings in a concentration-dependent manner. Although addition of diphenhydramine, ONO-3708, phentolamine, methysergide, atropine, and meclofenamate did not alter the contractile response to adrenotensin, removal of the endothelial cell layer significantly reduced this response. Moreover, precontraction of PA rings with adrenotensin selectively attenuated the pulmonary vasorelaxant response to ADM but not to other vasodilator substances, including isoproterenol, pinacidil, nifedipine, and adenosine. The present data suggest that adrenotensin acts in an endothelium-dependent manner to contract PA rings. Moreover, the present data suggest that adrenotensin may act in a modulatory manner to influence vasorelaxation in response to ADM, a sister proADM product.

A novel model to study the effects of burn lymph on pulmonary vascular hemodynamic variables.

OBJECTIVE To determine the effects of burn lymph on pulmonary hemodynamic variables. METHODS A balloon-tipped catheter was fluoroscopically passed from a jugular vein into the right lower lobe (RLL) pulmonary artery of rats, its distal lumen used to measure pulmonary artery pressure. Inflation allowed measurement of RLL wedge pressure, which represents pulmonary venous pressure. After inflation, the RLL underwent constant flow pump-perfusion with carotid artery blood. Preburn (n = 5) or post-burn (n = 6) dog lymph was infused into the RLL for 50 minutes. MEASUREMENTS Because perfusion flow rate was constant throughout the experiment, RLL changes in pulmonary artery pressure reflect changes in pulmonary vascular resistance. RESULTS Animals given preburn lymph had no alterations in RLL pulmonary hemodynamics. The immediate, significant (p < 0.005, analysis of variance) increases in RLL pulmonary artery pressure (16.2 +/- 2.3 mm Hg at baseline vs. 35.4 +/- 2.1 mm Hg at 30 minutes) and pulmonary vascular resistance (0.0 at baseline vs 1.37 +/- 0.24 at 30 minutes) after burn lymph injection persisted beyond infusion interruption. CONCLUSION The persistent pulmonary hypertensive response to postburn lymph warrants further investigation.