Differential effects of (+/-)-dobutamine and human alpha-CGRP on cardiac and on regional haemodynamics in conscious Long Evans rats

Abstract

1. Comparisons were made of the full haemodynamic profiles of the known cardiostimulant, (+/-)-dobutamine, and the putative inotropic peptide, human alpha-calcitonin gene-related peptide (human alpha-CGRP), in conscious, chronically-instrumented Long Evans rats. Both substances were administered continuously i.v. for 60 min at two doses ((+/-)-dobutamine, 2 and 10 mumol kg-1 h-1; human alpha-CGRP, 0.15 and 1.5 nmol kg-1 h-1). 2. In spite of their similar (small) effects on mean arterial blood pressure, the low doses of (+/-)-dobutamine and human alpha-CGRP influenced cardiac haemodynamics differently. Thus, (+/-)-dobutamine caused an increase in cardiac index (due to a tachycardia), accompanied by rises in peak aortic flow, maximum rate of rise of aortic flow (dF/dtmax) and total peripheral conductance. However, the latter waned during the infusion, and after the infusion there was a significant systemic vasoconstriction and reductions in peak aortic flow, dF/dtmax and stroke index. Such 'off' effects following dobutamine infusion have not been described previously. The infusion of the lower dose of human alpha-CGRP caused only a transient fall in central venous pressure. 3. The rise in total peripheral conductance during infusion of the lower dose of (+/-)-dobutamine was associated with increases in hindquarters and common and internal carotid vascular conductances. The fall in total peripheral conductance after infusion was associated with renal vasoconstriction. Although there was no significant change in total peripheral conductance during the infusion of the lower dose of human alpha-CGRP there were hindquarters and carotid vasodilatations together with mesenteric vasoconstriction. 4. Infusion of the higher dose of ( )-dobutamine had greater effects than the lower dose on all cardiac haemodynamic variables and additionally, increased stroke index. However, the negative cardiac haemodynamic effects following the offset of infusion were also enhanced in association with marked renal and mesenteric vasoconstrictions. While infusion of the higher dose of human alpha-CGRP increased cardiac index, peak aortic flow, dF/dtmax and total peripheral conductance, stroke index fell together with central venous pressure. 5. (+/-)-Dobutamine caused greater cardiostimulation and increases in hindquarters blood flow than did human alpha-CGRP. However, the latter at the higher dose caused substantially greater common and internal carotid hyperaemia than did (+/-)-dobutamine, possibly indicating a selective and additional effect of human alpha-CGRP on cranial blood flow. Furthermore, there were no adverse cardiovascular effects following infusion of human alpha-CGRP.