Altered blood pressure response to propyldazine after repeated oral administration in conscious normotensive dogs: role of the renin-angiotensin system.
The magnitude and the persistence of blood pressure reduction by propyldazine (PDZ) was investigated following treatment over a period of 4 days. The experiments were performed on 6 normotensive dogs trained to submit to puncture of the femoral artery and to stand quietly in a special frame over the experimental period of 7 to 8 hours. The first dose effect of orally administered PDZ (0.06, 0.29 and 1.42 mg/kg) on heart rate, arterial blood pressure and plasma renin activity (PRA) was compared with the effect of the substance after treatment at the same respective dosage twice daily over 4 days. The compound caused a dose-dependent decrease in blood pressure accompanied by dose-dependent increases in heart rate and PRA. With 0.06 mg/kg and 0.29 mg/kg PDZ a sustained effect on arterial blood pressure was observed, whereas with 1.42 mg/kg PDZ tolerance occurred after treatment over the 4-day period. A comparison with the effects observed previously with 1.42 and 7.1 mg/kg dihydralazine (DHZ) under identical conditions showed similar results with respect to dose-dependence of blood pressure and counterregulation (1). It is considered that with a low-dose regimen there would be no decrease in activity of PDZ, the long-term hypotensive efficacy of the drug thereby being guaranteed.
D000284:Administration, Oral; D000450:Aldosterone / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004078:Dihydralazine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D011724:Pyridazines / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000959:Antihypertensive Agents; D011724:Pyridazines; D000450:Aldosterone; D012083:Renin; C009978:propildazine; D004078:Dihydralazine