Hemodynamic effects of a new alpha- and beta-adrenergic receptor inhibitor with calcium entry blocking effects (CGS 10078B) in WKY and SHR rats.

The immediate acute hemodynamic effects of CGS 10078B, a new agent with combined alpha- and beta-adrenergic antagonist with slow channel calcium entry blocking effects, were studied in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), total peripheral resistance index (TPRI), and regional hemodynamic measurements were determined before and two hours after its administration (10 mg/kg, gavage) using the combined radioactive reference sample and microsphere techniques (85SR and 141Ce). The agent significantly reduced MAP (168 +/- 5 to 158 +/- 5 mm Hg; p less than 0.02) after 20 minutes without changing HR in SHR. After two hours MAP, HR, and Cl were significantly reduced without change in TPRI. Only Cl decreased (p less than 0.05) in WKY, presumably from its beta receptor antagonist effects. Blood flow to the major organs (eg, heart, brain, and kidneys) was maintained in both groups of rats. These hemodynamic effects reflect the combined actions of this new agent and suggest its potential value for the treatment of hypertension.