Effect of the type IV phosphodiesterase inhibitor Ro 20-1724 on catecholamine-induced alterations in regional vascular resistance and regional blood flow.

Abstract

Type IV phosphodiesterase inhibitors have been studied in multiple disease processes that commonly afflict patients who are treated with catecholamine infusions. To examine whether type IV phosphodiesterases alter catecholamine-induced changes in systemic and regional hemodynamic parameters, we examined the effects of Ro 20-1724 on rats during dobutamine, epinephrine, isoproterenol, and norepinephrine infusions. Twenty-six Sprague-Dawley rats received either Ro 20-1724 or vehicle. After central and regional hemodynamic monitoring was initiated, animals received increasing doses of two of the four catecholamines. In the absence of catecholamines, Ro 20-1724 infusion caused a significant increase in heart rate and a trend toward an increase in superior mesenteric artery blood flow. Ro 20-1724 attenuated the increase in blood pressure caused by epinephrine but had no effect on the dobutamine-, isoproterenol-, or norepinephrine-induced changes in blood pressure. Ro 20-1724 had no effect on catecholamine-induced changes in renal, carotid, and hindquarter vascular resistance but did attenuate the decrease in superior mesenteric artery vascular resistance caused by isoproterenol. Type IV phosphodiesterase inhibition in combination with catecholamines has no adverse effects on regional hemodynamics; however, it can inhibit the ability of epinephrine infusion to increase blood pressure.