دورية أكاديمية
The negative inotropic effect of beta(3)-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle
| العنوان: | The negative inotropic effect of beta(3)-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle |
|---|---|
| المؤلفون: | Gauthier, C, Leblais, V, Kobzik, L, Trochu, JN, Khandoudi, N, Bril, A, Balligand, Jean-Luc, Le Marec, H |
| المساهمون: | UCL |
| المصدر: | Journal of Clinical Investigation, Vol. 102, no. 7, p. 1377-1384 (1998) |
| بيانات النشر: | Rockefeller Univ Press |
| سنة النشر: | 1998 |
| المجموعة: | DIAL@UCL (Université catholique de Louvain) |
| مصطلحات موضوعية: | beta-adrenoceptors, human myocardium, nitric oxide, cGMP, contractility |
| الوصف: | beta(1)- and beta(2)-adrenoceptors in heart muscle cells mediate the catecholamine-induced increase in the force and frequency of cardiac contraction, Recently, in addition, we demonstrated the functional expression of beta(3)-adrenoceptors in the human heart. Their stimulation, in marked contrast with that of beta(1)- and beta(2)-adrenoceptors, induces a decrease in contractility through presently unknown mechanisms. In the present study, we examined the role of a nitric oxide (NO) synthase pathway in mediating the beta(3)-adrenoceptor effect on the contractility of human endomyocardial biopsies. The negative inotropic effects of a beta(3)-adrenoceptor agonist, BRL 37344, and also of norepinephrine in the presence of alpha- and beta(1-2)-blockade were inhibited both by a nonspecific blocker of NO, methylene blue, and two NO synthase (NOS) inhibitors, L-N-monomethyl-arginine and L-nitroarginine-methyl ester, The effect of the NOS inhibitors was reversed by an excess of L-arginine, the natural substrate of NOS, but not by D-arginine. Moreover, the effects of the beta(3)-adrenoceptor agonist on contractility were associated with parallel increases in the production of NO and intracellular cGMP, which were also inhibited by NOS inhibitors, Immunohistochemical staining of human ventricular biopsies showed the expression of the endothelial constitutive (eNOS), but not the inducible (iNOS) isoform of NOS in both ventricular myocytes and endothelial cells. These results demonstrate that beta(3)-adrenoceptor stimulation decreases cardiac contractility through activation of an NOS pathway, Changes in the expression of this pathway may alter the balance between positive and negative inotropic effects of catecholamines on the heart potentially leading to myocardial dysfunction. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0021-9738 1558-8238 |
| العلاقة: | boreal:45025; http://hdl.handle.net/2078.1/45025Test; urn:ISSN:0021-9738; urn:EISSN:1558-8238 |
| DOI: | 10.1172/JCI2191 |
| الإتاحة: | https://doi.org/10.1172/JCI2191Test http://hdl.handle.net/2078.1/45025Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E4FF6C39 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00219738 15588238 |
|---|---|
| DOI: | 10.1172/JCI2191 |