| First Author | Kisanuki YY | Year | 2010 |
| Journal | Hypertension | Volume | 56 |
| Issue | 1 | Pages | 121-8 |
| PubMed ID | 20516397 | Mgi Jnum | J:196635 |
| Mgi Id | MGI:5488884 | Doi | 10.1161/HYPERTENSIONAHA.109.138701 |
| Citation | Kisanuki YY, et al. (2010) Low blood pressure in endothelial cell-specific endothelin 1 knockout mice. Hypertension 56(1):121-8 |
| abstractText | Endothelin (ET) 1 is a potent vasoconstrictor peptide produced by vascular endothelial cells and implicated in various pathophysiologic states involving abnormal vascular tone. Homozygous ET-1 null mice have craniofacial and cardiac malformations that lead to neonatal death. To study the role of ET-1 in adult vascular physiology, we generated a mouse strain (ET-1(flox/flox);Tie2-Cre mice) in which ET-1 is disrupted specifically in endothelial cells. ET-1 peptide levels in plasma, heart, lung, kidney, and brain homogenates were reduced by 65% to 80% in these mice. mRNA levels for ET receptors were unaltered except that the ET(A) receptor mRNA was upregulated in the heart. ET-1(flox/flox);Tie2-Cre mice had mean blood pressures 10 to 12 mm Hg lower than genetic controls. In contrast, the blood pressure of mice systemically heterozygous for the ET-1 null allele (ET-1(dlox/+) mice) was unchanged compared with wild-type littermates. Despite the lower basal blood pressure, acute pharmacological responses to angiotensin II, captopril, phenylephrine, bradykinin, N(G)-nitro-L-arginine methyl ester, and exogenous ET-1 were normal in ET-1(flox/flox);Tie2-Cre mice. These results support an essential role of endothelial-derived ET-1 in the maintenance of basal vascular tone and blood pressure. Normal pharmacological responses of ET-1(flox/flox);Tie2-Cre mice suggest that the renin-angiotensin system, the adrenergic system, and NO are not significantly altered by endothelial ET-1. Taken in conjunction with other lines of genetically altered mice, our results provide evidence for a paracrine vasoregulatory pathway mediated by endothelial cell-derived ET-1 acting on the vascular smooth muscle ET(A) receptor. |
