Vasodilatory activity of novel carbamate derivatives of isatin.
Clin Exp Pharmacol Physiol
; 35(9): 1091-6, 2008 Sep.
Article
em En
| MEDLINE
| ID: mdl-18505449
ABSTRACT
Isatin (1H-indole-2,3 dione) is an endogenous compound that may act as a physiological regulator of muscle contraction by reducing cGMP production by inhibition of guanylyl cyclase (GC) activity. Intracellular cGMP levels can regulate the contractile response of smooth muscle. Therefore, in the present study we investigated the effects of seven novel carbamate derivatives of isatin, namely C1-C7, on the contractility of aortic rings from Wistar rats. Carbamates C1 and C6 most effectively promoted endothelium-dependent relaxation of aortic rings pretreated with 10 micromol/L phenylephrine (PE) to induce contraction. The concentration of the C1 and C6 carbamates necessary to reduce PE-induced aortic contraction by 50% (IC(50)) was 5.6 +/- 1.0 and 48.4 +/- 3.4 micromol/L, respectively. Carbamate derivative-induced vasodilation required an intact endothelium, which is responsible for nitric oxide (NO) release. Pretreatment of rings with 100 micromol/L naloxone or 10 micromol/L atropine prevented the C1- and C6-mediated vascular relaxation, indicating that the vasodilatory activity was dependent on the activation of opioid or muscarinic receptors, respectively. The results of our studies provide insights into the role of novel carbamates in the regulation of vascular tone. Carbamates could stimulate NO synthesis, which induces vasodilation primarily by stimulation of GC and cGMP production. Taken together, our findings suggest that carbamate derivative-induced vasodilation may be considered an alternative treatment for primary and/or secondary hypertension.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatação
/
Vasodilatadores
/
Carbamatos
/
Isatina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Clin Exp Pharmacol Physiol
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Brasil