Cardiovascular effects of two new calcium antagonists, PY 108-068 and PN 200-110, in conscious spontaneously hypertensive rats.
1. The acute cardiovascular effects of PY 108-068 and PN 200-110 were studied by means of a computerized analysis of the intra-aortic blood pressure (BP) recorded continuously for 26 h in conscious unrestrained spontaneously hypertensive rats. Both compounds were studied at three doses (50, 100 and 200 micrograms kg-1) and each dose was administered intravenously 5 times (09 h 00 min, 14 h 00 min, 19 h 00 min, 24 h 00 min and 09 h 00 min). Baroreflex sensitivity was measured 1 h following the last injection. 2. The two compounds were found to induce rapid (3 min) and dose-dependent falls in BP. After the first administration, these decreases reached -20% and -35% for systolic BP (SBP) and diastolic BP (DBP) respectively with PY 108-068 (200 micrograms kg-1) and -25% and -45% for SBP and DBP respectively with PN 200-110 (200 micrograms kg-1). 3. The duration of the reduction in BP increased with the dose and was much longer for PN 200-110 (180 min for SBP) than for PY 108-068 (20 min for SBP). 4. A tachycardia was associated with the decrease in BP which did not differ at 200 micrograms kg-1 between PY 108-068 (+ 108 beats min-1) and PN 200-110 (+ 103 beats min-1). Baroreflex sensitivity was not significantly increased by either drug. 5. The 5 repeated injections of PY 108-068 and PN 200-110 evoked similar responses. 6. In conclusion, both compounds exhibited marked hypotensive properties. PN 200-110 appeared to be more suitable for further development since its effects were found to be greater and much longer lasting than those of PY 108-068.
Barrès
C
C
Department of Physiology and Clinical Pharmacology (UA CNRS 606), Faculty of Pharmacy, Lyon, France.
Cerutti
C
C
Morin
B
B
Sassard
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D017275:Isradipine; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012018:Reflex / Q000187:drug effects
D002121:Calcium Channel Blockers; D010069:Oxadiazoles; D010656:Phenylephrine; D005996:Nitroglycerin; D009543:Nifedipine; C034600:darodipine; D017275:Isradipine