In vivo and in vitro effects of cicletanine in spontaneously hypertensive rats

Oral treatment for 2 weeks with cicletanine [1,3-dihydro-6-methyl-7-hydroxy-3-(4-chloro-phenyl)furo(3,4-c)pyridine] at 30 mg/kg/day delayed the onset of hypertension in spontaneously hypertensive rats (SHR) (15.7 mmHg, p less than 0.001). This antihypertensive effect was increased when the animals w...

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Published inDrugs under experimental and clinical research Vol. 14; no. 2-3; p. 89
Main Authors Auguet, M, Guillon, J M, Delaflotte, S, Le Hegarat, M, Pirotzky, E, Clostre, F, Braquet, P
Format Journal Article
LanguageEnglish
Published Switzerland 1988
Subjects
Angiotensin II - pharmacology
Animals
Antihypertensive Agents - administration & dosage
Antihypertensive Agents - pharmacology
Antihypertensive Agents - therapeutic use
Aorta, Thoracic - drug effects
Blood Pressure - drug effects
Calcium - metabolism
Diuretics - administration & dosage
Diuretics - pharmacology
Diuretics - therapeutic use
Hypertension - drug therapy
In Vitro Techniques
Male
Muscle Contraction - drug effects
Muscle, Smooth, Vascular - drug effects
Phenylephrine - pharmacology
Pyridines
Rats
Rats, Inbred SHR
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Summary:Oral treatment for 2 weeks with cicletanine [1,3-dihydro-6-methyl-7-hydroxy-3-(4-chloro-phenyl)furo(3,4-c)pyridine] at 30 mg/kg/day delayed the onset of hypertension in spontaneously hypertensive rats (SHR) (15.7 mmHg, p less than 0.001). This antihypertensive effect was increased when the animals were maintained on a high-salt diet (40.8 mmHg, p less than 0.001). The ability of cicletanine to alter calcium movements in phenylephrine (PE)- and angiotensin II (ANGIO)-triggered contraction was tested on isolated SHR aorta. PE (1 microM) and ANGIO (0.1 microM) induced a phasic contraction in calcium-free medium due to intracellular calcium release. Upon addition of calcium (2.5 mM) a second sustained (PE) or biphasis (ANGIO) contraction was observed. This second contraction was dependent on extracellular calcium influx. Cicletanine (0.1-0.3 mM) both reduced the phasic (77%, p less than 0.001 for PE; 68%, p less than 0.05 for ANGIO with cicletanine 0.3 mM) and the second contraction elicited by the two agonists (27%, p less than 0.001 for PE; 84%, p less than 0.001 for ANGIO with cicletanine 0.3 mM). These results suggest that in addition to its stimulatory effect on prostaglandin, a direct vascular action of cicletanine could also be involved in the antihypertensive properties of the drug.
ISSN:0378-6501