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  • Title: Acute antihypertensive effects of the new generation calcium antagonist 3-pyridine carboxylic acid 5-[(cyclopropylamino)-carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitrophen yl) octyl ester on conscious spontaneously hypertensive rats and renal hypertensive rats.
    Author: Hojo M, Tanaka Y, Katayama O, Teramoto N.
    Journal: Arzneimittelforschung; 1993 Aug; 43(8):847-51. PubMed ID: 8216440.
    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)
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