The present study was undertaken to examine the effect of parathyroid hormone-related peptide (PTHrP) on the vascular tone as well as the expression of its mRNA in the cardiovascular system and its regulation in response to systemic hypertension in Sprague-Dawley rats. In aortic rings precontracted with 0.3 mu M norepinephrine PTHrP(1-34) caused a dose-dependent relaxation with the maximal response of 33% being observed at 10(-6) M. PTHrP was nearly equipotent to PTH or CGRP in the vasodilatory action. Ribonuclease protection assay and Northern blot analysis demonstrated that PTHrP mRNA levels in the heart and aorta were increased as a result of systemic hypertension induced by constant infusion of angiotensin II and salt loading. The results of our in vivo studies suggest an autocrine/paracrine role for PTHrP as a local regulator of the vascular tone. (C) 1995 Academic Press. Inc.