Endothelial Functional Changes during The Development of Hypertension in Spontaneously Hypertensive Rats
| Autor: | Chin-Yen Liu, 柳錦燕 |
|---|---|
| Rok vydání: | 2001 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 89 Hypertension is a multifactorial disease that may result from interaction of neural, hormonal, and intracellular factors. Until now, the exact pathogenic mechanisms are still unclear. The endothelium plays a central role in blood pressure homeostasis. In response to stimulation by agonists, the endothelium produces endothelium-derived nitric oxide (EDNO), endothelium-derived hyperpolarizing factor (EDHF) or prostacyclin (PGI2) through the elevation of intracellular calcium ([Ca2+]i) and induces vasodilaiton. However, the detailed role of endothelial [Ca2+]i in blood pressure regulation is poorly understood, and the roles of EDNO and EDHF in spontaneously hypertensive rats (SHR) are contradictory. In this study, we used our newly developed technique to simultaneously monitor both endothelial [Ca2+]i signaling and vasodilating responses in thoracic aortas of SHR and Wistar-Kyoto rats (WKY) of various ages (ie, 6, 14 or 28 weeks old). Acetylcholine (ACh)-induced endothelial [Ca2+]i elevation and concomitant vasorelaxation responses in phenylephrine- precontracted vessel segments were determined. To elucidate the roles of EDNO, EDHF or PGI2 in these responses, some preparations were pretreated with the following inhibitors before the ACh experiments: N-nitro-L- arginine methyl ester (L-NAME), tetraethylammonium (TEA), or indomethacin. Our results showed that 1) the vasodilating response to ACh was enhanced in 14-wk-old SHR when the blood pressure initiate to increase, possibly due to greater release of NO and EDHF; 2) when the blood pressure rised up to about 200 mmHg, ACh-induced vasodilation maked no difference between 28-wk-old SHR and age-matched WKY; 3) EDHF contribute little in vasodilation of 6- and 28-wk-old SHR; 4) the basal endothelial [Ca2+]i in 14-wk-old SHR was higher than those in WKY of the same age; 5) when compare with 28-wk-old WKY, the basal endothelial [Ca2+]i in 28-wk-old SHR was the same. In summary, both the basal [Ca2+]i and ACh-induced vasorelaxation were enhanced in 14-wk-old SHR when their blood pressure just increased. In 28-wk-old SHR whose blood pressure already reached plateau, both the basal endothelial [Ca2+]i and ACh-induced vasorelaxation were reduced to similar levels like those in WKY of the same age. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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