Abstract |
The acute antihypertensive effects of 3-pyridine carboxylic acid 5-[(cyclo-propylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitroph eny l) octyl ester (NP-252, CAS 132031-81-3) administered orally to conscious spontaneously hypertensive rats (SHRs) and renal hypertensive rats (RHRs) were evaluated using the impedance plethysmographical technique as a modified tail cuff method, and compared with those of nifedipine (NF). In the fitness test of this indirect method, the average value of blood pressure (BP) measured in 7 conscious SHRs was 201 +/- 6.9 mmHg. This value showed good correlation with that (201 +/- 8.8 mmHg) of systolic BP measured by the direct method in the same animals. In the comparative study of antihypertensive activities of the compounds on both models of hypertension using this method, NP-252 and NF dose-dependently lowered BP having a different peak time and restoration after dosing. Therefore, the antihypertensive activities were compared using a 20% effective dose (ED20) for producing hypotension, and the ED20 values of NP-252 and NF were 2.55 and 2.00 mg/kg in SHRs, and 1.25 and 0.67 mg/kg in RHRs, respectively. Moreover, the duration of actions of the compounds were evaluated by the simulated duration time (SDT) which was calculated from the peak time of BP-fall and the pharmacological half life time for the maximum BP-fall and the SDT values of NP-252 and NF were 1.85-4.70 and 0.90-0.75 h in SHRs, and 3.30-12.80 and 0.57-6.90 h in RHRs, respectively. Also, the BP-falls by the compounds were accompanied by an increase in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
|
Authors | M Hojo, Y Tanaka, O Katayama, N Teramoto |
Journal | Arzneimittel-Forschung
(Arzneimittelforschung)
Vol. 43
Issue 8
Pg. 847-51
(Aug 1993)
ISSN: 0004-4172 [Print] Germany |
PMID | 8216440
(Publication Type: Comparative Study, Journal Article)
|
Chemical References |
- Antihypertensive Agents
- Calcium Channel Blockers
- Dihydropyridines
- NP 252
- Nifedipine
|
Topics |
- Animals
- Antihypertensive Agents
(pharmacology)
- Blood Pressure
(drug effects)
- Calcium Channel Blockers
(pharmacology)
- Dihydropyridines
(pharmacology)
- Dose-Response Relationship, Drug
- Half-Life
- Heart Rate
(drug effects)
- Hypertension
(physiopathology)
- Hypertension, Renal
(physiopathology)
- Male
- Nifedipine
(pharmacology)
- Rats
- Rats, Inbred SHR
- Rats, Wistar
|