Use of a new pulsatile perfused rat aorta preparation to study the characteristics of the vasodilator effect of parathyroid hormone.

Both the native hormone and the aminoterminal 1-34 peptide of parathyroid hormone [PTH-(1-34)] are potent vasodilators of the coronary and hepatic circulations and, relatedly, produce marked hypotensive effects in a variety of animal species. In this report, a new technique for studying vasoactive substances was used to determine the nature of the vasodilator response of the aminoterminal peptide. The technique, an alternative to classical cylindrical segment or helical strip approaches, involved perfusion of a 4 to 5 cm segment of rat thoracic aorta at a constant flow rate with a circumferentially applied pulsatile "systolic" pressure of 100 mm Hg. Changes in perfusion pressure were indicative of changes in vascular resistance. The perfusate consisted of oxygenated physiological salt solution. Aortas were precontracted with high [KCl], norepinephrine, phenylephrine or arginine vasopressin. PTH-(1-34) elicited a concentration-related relaxation of vessels precontracted with the alpha agonists or [arg8]-vasopressin, but did not inhibit high K+ (3.5 x 10(-2) M)-induced contractions over the same dose range. Inhibition of prostaglandin biosynthesis with indomethacin did not alter the vasorelaxant properties of the peptide fragment. Endothelium-dependency of the PTH-(1-34)-induced vasorelaxant effect was assessed in untreated aortas and in tissues pretreated with saponin. Aortas pretreated with saponin, in which both scanning and transmission electron microscopy revealed extensive damage to or loss of endothelium, relaxed in a manner indistinguishable from nontreated control vessels. Thus, PTH-(1-34) relaxed precontracted perfused rat aortas in dose-dependent fashion. The vasorelaxant effects of the peptide fragment involved preferential relaxation of pharmacomechanically coupled vessels, and were not mediated by vasodilator prostaglandins or other specific endothelium-dependent mechanisms.