Systemic and regional hemodynamic effects of E614 (tripamide) as studied in conscious SHR

Experiments were conducted on 53 conscious young male spontaneously hypertensive rats utilizing radiolabeled microspheres to analyze the acute and chronic hemodynamic effects of a newly synthesized antihypertensive drug, E614. The hemodynamic variables were observed on the 1st and 6th days of E614 treatment (p.o., once daily) in separate groups of rats. When the drug was given at a smaller dose (10 mg/kg body weight) over 6 days, the hypotensive action of E614 was found to be due mainly to a reduction of the total peripheral vascular resistance with no significant change in the cardiac output (CO). A supra-pharmacological dose (100 mg/kg), however, lowered the mean arterial pressure (AP) due mainly to a significant reduction of the CO in both the acute and chronic treatments. We found little influence of the drug on heart rate, and the coronary and renal vascular beds in any of the present experimental settings. The cerebral blood flow appeared not to change significantly unless the AP fell to such an extent that a fall in cerebral blood flow took place despite the autoregulatory mechanism of the brain blood vessels. The tissue perfusion was also well preserved in the gastrointestinal tract.