García-Villalón A L, Monge L, Fernández N, Sánchez M A, Martínez M A, Gómez B, Diéguez G
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Cardiovasc Res. 2000 Jan 14;45(2):463-9. doi: 10.1016/s0008-6363(99)00279-5.
To analyse the effects of endothelin-1 and vasopressin on the sympathetic vasoconstriction during hypertension.
Electrical field stimulation (4 Hz) was applied to isolated, 2 mm segments of the tail artery from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats prepared for isometric tension recording.
The contraction to electrical stimulation was potentiated by endothelin-1 (10(-10)-10(-8) M) in arteries from WKY but not from SHR, and by vasopressin (10(-12)-10(-10) M) more markedly in arteries from WKY than from SHR. The potentiation by endothelin-1 was reduced more markedly by the antagonist of endothelin ETA receptors BQ-123 (10(-5) M) than by the endothelin ETB receptor antagonist BQ-788 (10(-5) M). The potentiation by vasopressin was reduced by the antagonist of vasopressin V1 receptors d(CH2)5Tyr(Me)AVP (10(-7) M), but not by the vasopressin V2 receptor antagonist d(CH2)5D-Ile2, Ile4AVP (10(-7) M). The blocker of L-type calcium channels verapamil (10(-5) M) reduced the potentiation by both endothelin-1 and vasopressin in arteries from WKY rats, and increased the potentiation by vasopressin in arteries from SHR. Noradrenaline (10(-8)-10(-4) M) contraction was not modified by endothelin-1 (3 x 10(-9) M) or vasopressin (3 x 10(-11) M), and contraction to endothelin-1 (10(-9)-10(-7) M) and vasopressin (10(-10)-10(-7) M) was lower in arteries from SHR than from WKY rats.
(1) The potentiation by endothelin-1 and vasopressin of the sympathetic vasoconstriction, probably due to increased release of noradrenaline, is impaired during hypertension, and (2) this potentiation is mediated mainly by endothelin ETA receptors, and by vasopressin V1 receptors, in both WKY and SHR, and for both peptides it is mediated by L-type calcium channels in arteries from normotensive but not in those from hypertensive animals.
分析内皮素 -1 和血管升压素对高血压期间交感神经血管收缩的影响。
对用于等长张力记录的自发性高血压（SHR）大鼠和正常血压的Wistar - Kyoto（WKY）大鼠分离出的2毫米尾动脉段施加电场刺激（4赫兹）。
内皮素 -1（10⁻¹⁰ - 10⁻⁸ M）增强WKY大鼠动脉对电刺激的收缩反应，但对SHR大鼠动脉无此作用；血管升压素（10⁻¹² - 10⁻¹⁰ M）增强WKY大鼠动脉对电刺激的收缩反应比SHR大鼠更明显。内皮素 -1 受体拮抗剂BQ - 123（10⁻⁵ M）比内皮素ETB受体拮抗剂BQ - 788（10⁻⁵ M）更显著地降低内皮素 -1 的增强作用。血管升压素受体拮抗剂d(CH2)5Tyr(Me)AVP（10⁻⁷ M）降低血管升压素的增强作用，但血管升压素V2受体拮抗剂d(CH2)5D - Ile2, Ile4AVP（10⁻⁷ M）无此作用。L型钙通道阻滞剂维拉帕米（10⁻⁵ M）降低WKY大鼠动脉中内皮素 -1 和血管升压素的增强作用，并增强SHR大鼠动脉中血管升压素的增强作用。去甲肾上腺素（10⁻⁸ - 10⁻⁴ M）收缩不受内皮素 -1（3×10⁻⁹ M）或血管升压素（3×10⁻¹¹ M）影响，且SHR大鼠动脉对内皮素 -1（10⁻⁹ - 10⁻⁷ M）和血管升压素（10⁻¹⁰ - 10⁻⁷ M）的收缩反应低于WKY大鼠。
（1）高血压期间，内皮素 -1 和血管升压素对交感神经血管收缩的增强作用（可能由于去甲肾上腺素释放增加）受损；（2）在WKY和SHR大鼠中，这种增强作用主要由内皮素ETA受体和血管升压素V1受体介导，对于这两种肽，在正常血压动物的动脉中由L型钙通道介导，而在高血压动物的动脉中则不然。
