Cardiovascular and renal actions of AHR-16303B, an antagonist of 5-HT2 receptors and calcium channels, in hypertensive and normotensive rats.
The cardiovascular and renal responses to AHR-16303B, a novel antagonist of 5-hydroxytryptamine (5-HT2) receptors and calcium channels, were examined in spontaneously hypertensive (SHR) and normotensive rats (NTR) and compared with verapamil and ritanserin. In SHR, AHR-16303B (10-300 mg/kg orally, p.o.) produced dose-related reductions in mean arterial blood pressure (MABP), accompanied by modest isokaliuretic diuresis and unchanged heart rate (HR). In NTR, 10-30 mg/kg p.o. AHR-16303B had no effect on MABP or renal excretory function; 100 and 300 mg/kg reduced MABP but had only transient effects on HR; 100 mg/kg produced antidiuresis in NTR. Both strains of rats tolerated doses of AHR-16303B as high as 300 mg/kg. In both SHR and NTR, verapamil (10-100 mg/kg p.o.) produced dose-related reductions in MABP, antinatriuresis at 60 and 100 mg/kg, and variable effects on HR. Oral ritanserin had no effect on MABP of SHR or NTR at 3 or 10 mg/kg. AHR-16303B is unique in that it simultaneously antagonizes 5-HT2 receptors and produces safe and effective reduction of elevated BP without altering HR or triggering renal compensatory antidiuresis. At effective 5-HT2/calcium antagonistic doses, AHR-16303B has no effect on cardiorenal homeostasis in normotensive animals.
Barrett
R J
RJ
Department of Pharmacology, A. H. Robins Research Laboratories, Richmond, Virginia.
Wright
K F
KF
Allen
A D
AD
Taylor
D R
DR
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects*; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011427:Propiophenones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D016713:Ritanserin; D012702:Serotonin Antagonists; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010880:Piperidines; D011427:Propiophenones; D012702:Serotonin Antagonists; C068453:AHR 16303B; D016713:Ritanserin; D014700:Verapamil