EFFECT OF THE TYPE-IV PHOSPHODIESTERASE INHIBITOR RO 20-1724 ON CATECHOLAMINE-INDUCED ALTERATIONS IN REGIONAL VASCULAR-RESISTANCE AND REGIONAL BLOOD-FLOW

Type TV phosphodiesterase inhibitors have been studied in multiple dis ease processes that commonly afflict patients who are treated with cat echolamine infusions. To examine whether type TV phosphodiesterases al ter catecholamine-induced changes in systemic and regional hemodynamic parameters, we examined the effects of Ro 20-1724 on rats during dobu tamine, epinephrine, isoproterenol, and norepinephrine infusions. Twen ty-six Sprague-Dawley rats received either Ro 20-1724 or vehicle. Afte r central and regional hemodynamic monitoring was initiated, animals r eceived increasing doses of two of the four catecholamines. In the abs ence of catecholamines, Ro 20-1724 infusion caused a significant incre ase in heart rate and a trend toward an increase in superior mesenteri c artery blood flow. Ro 20-1724 attenuated the increase in blood press ure caused by epinephrine but had no effect on the dobutamine-, isopro terenol-, or norepinephrine-induced changes in blood pressure. Ro 20-1 724 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 catecholami nes has no adverse effects on regional hemodynamics; however, it can i nhibit the ability of epinephrine infusion to increase blood pressure.