Hemopressin, a hemoglobin fragment, dilates the rat systemic vascular bed through release of nitric oxide.

The present study was undertaken to investigate the effects of intravenous (i.v.) administration of rat hemopressin (rHP), 30-1000 microg/kg, on systemic arterial pressure (SAP), cardiac output (CO) and systemic vascular resistance (SVR) in the anesthetized rat. Bolus i.v. injections of rHP produced mild decreases in SAP that were dose-dependent. Since CO was not altered, the decreases in SAP reflect reductions in SVR. The systemic vasodilator response to rHP was not subject to tachyphylaxis. The systemic vasodilator response to rHP was abolished by L-nitro-arginine methylester (L-NAME) but was not altered by meclofenamate. In addition, rHP lacked direct contractile and relaxant activity on isolated rat aortic rings (AA) and pulmonary arterial rings (PA). The present data suggest rHP dilates the rat systemic vascular bed through the endogenous release of nitric oxide (NO) independent of the formation of cyclooxygenase products including prostacyclin. It is possible rHP acts as an endogenous vasodilator substance to regulate local blood flow during clinical states of altered red cell turnover, microvascular disease and hemolysis.

Intermedin/adrenomedullin-2 dilates the rat pulmonary vascular bed: dependence on CGRP receptors and nitric oxide release.

Intermedin/adrenomedullin-2 (IMD/AM2) is a 47 amino acid peptide formed by enzymatic degradation of preprointermedin. The present study was undertaken to investigate the effects of rat IMD (rIMD) in the isolated buffer perfused rat lung (IBPR) under resting conditions and under conditions of elevated pulmonary vasoconstrictor tone (PVT). Under resting conditions in the IBPR, rIMD had little or no activity. When PVT was actively increased by infusion of U46619, bolus injection of IMD decreased pulmonary arterial pressure (PAP) in a dose-dependent manner. Since the pulmonary perfusion rate and left atrial pressure were constant, these reductions in PAP directly reflect reductions in pulmonary vascular resistance (PVR). The pulmonary vasodilator response to rIMD, when compared to calcitonin gene-related peptide (CGRP) on a molar basis, was greater at the lowest and midrange doses. The degree of inhibition by CGRP8-37 on pulmonary vasodilator response to rIMD was significantly less when compared to CGRP. Pretreatment with L-nitro-arginine-methyl ester (L-NAME), unlike meclofenamate and glybenclamide, significantly reduced the pulmonary vasodilator responses to rIMD. rIMD administration induced cross-tachyphylaxis to the pulmonary vasodilator response to CGRP whereas CGRP administration did not alter the ability of rIMD to dilate the IBPR. Pulmonary vasodilator responses to repeated injections of rIMD did not undergo tachyphylaxis. The present data demonstrate rIMD possesses direct vasodilator activity in the rat pulmonary vascular bed. The present data suggest activation of CGRP1 receptors and release of nitric oxide (NO*) mediate the pulmonary vasodilator response to rIMD whereas cyclooxygenase products and KATP channels do not contribute to the pulmonary vasodilator response to rIMD. The ability of rIMD to induce heterologous desensitization of CGRP1 receptor activation, to retain much of its pulmonary vasodilator activity after inhibition of CGRP1 receptors, and to lack homologous desensitization together suggests the pulmonary, unlike the systemic, vasodilator response to rIMD may depend on other vasodilator mechanisms including receptors in the calcitonin-receptor-like-receptor (CRLR) family.

A system for measurement and calibration of nonorthogonal joints and limbs in humans.

Human limbs are a multilinked system in which the revolute joints are not orthogonal to the limb segments or to each other. The standard method for movements of multilinked systems is the Denavit-Hartenberg (DH) representation, which is useful for orthogonal systems. When applied to non-orthogonal systems, the DH representation projects the reference frames outside of the limb segments. Computer graphics techniques move arrays of points in bodies that move about arbitrary revolute joints. This computational model has been modified to calculate both position (X, Y, Z) and orientation (yaw, pitch, and roll) of limbs and their individual segments. This method allows a simplified representation for the kinematics of animal limbs.