| First Author | Faraci FM | Year | 1998 |
| Journal | Am J Physiol | Volume | 274 |
| Issue | 2 Pt 2 | Pages | H564-70 |
| PubMed ID | 9486260 | Mgi Jnum | J:45784 |
| Mgi Id | MGI:1196114 | Doi | 10.1152/ajpheart.1998.274.2.H564 |
| Citation | Faraci FM, et al. (1998) Responses of carotid artery in mice deficient in expression of the gene for endothelial NO synthase. Am J Physiol 274(2 Pt 2):H564-70 |
| abstractText | We examined the hypotheses that responses to acetylcholine are impaired and responses to NO are enhanced in carotid artery from mice made deficient in endothelial nitric oxide synthase (eNOS) by gene targeting (eNOS-deficient mice). We also tested the hypothesis that deletion of one copy of the eNOS gene is sufficient to alter vascular responses. Vessels were studied in vitro from heterozygous (+/-) and homozygous (-/-) eNOS-deficient mice as well as wild-type [eNOS(+/+)] littermates. After precontraction with prostaglandin F2 alpha, acetylcholine produced marked relaxation of carotid arteries in eNOS(+/+) mice, with impaired vasorelaxation in eNOS(+/-) mice. For example, 1 microM acetylcholine relaxed carotid arteries by 55 +/- 5% (mean +/- SE) in eNOS(+/-) mice (n = 13) compared with 83 +/- 3% in eNOS(+/+) mice (n = 14, P < 0.001 vs. +/-). In contrast, acetylcholine caused no relaxation in carotid arteries from eNOS(-/-) mice (P < 0.001 vs. +/+ and +/-). Relaxation of the carotid artery in response to nitroprusside [a nitric oxide (NO) donor] was enhanced (P < 0.001) in eNOS-deficient mice. For example, in response to 10 nM nitroprusside, the carotid artery relaxed by 18 +/- 2% in eNOS(+/+) mice (n = 14), 33 +/- 2% in eNOS(+/-) mice (n = 13), and 47 +/- 4% in eNOS(-/-) mice (n = 5). Thus relaxation of the carotid artery is impaired with acetylcholine and enhanced with the NO donor nitroprusside in eNOS-deficient mice. Enhanced responses to NO may represent a compensatory response expressed in the absence of eNOS. The findings that vascular responses to acetylcholine and NO are altered in eNOS(+/-) mice compared with those observed in eNOS(+/+) mice suggest a gene-dosing effect. |
