Abstract

It has been demonstrated previously that parathyroid hormone-related protein (PTHrp) has potent vasodilatory and cardiac stimulatory properties. However, the systemic and regional hemodynamic effects of PTHrp are unknown. In order to characterize these effects, we utilized the radioactive microsphere technique to examine the systemic and regional hemodynamics before and 2 min after the i.v. bolus administration of 0.03, 0.3 and 3.0 micrograms/ml/100 g b.wt. of PTHrp in conscious, unrestrained, normal rats. These effects were compared to those of synthetic rat parathyroid hormone (PTH), an agent known to affect cardiovascular function. PTHrp and PTH similarly and significantly decreased mean systemic blood pressure and total peripheral resistance but increased heart rate and cardiac output, all in a dose-dependent manner. Both peptides increased blood flow and decreased vessel resistance in regional vascular beds such as skin and heart. Renal resistance was reduced by PTH and PTHrp, but renal blood flow was not altered. Conversely, both peptides significantly decreased blood flow and increased vascular resistance to the splanchnic organs. Thus, PTHrp as well as PTH, preserved and enhanced cardiac function in the face of reduced systemic blood pressure while maintaining renal flow. These features are highly desirable in the treatment of some severe cardiovascular abnormalities. These results are consistent with the hypothesis that PTHrp may play an important hormonal, autocrine or paracrine role in systemic and regional blood flow regulation.