Effect of Estrogen Replacement on Vascular Responsiveness in Ovariectomized Spontaneously Hypertensive Rat.
10.4070/kcj.2000.30.4.528
- Author:
Bonggwan SEO
;
Dong Ju CHOI
;
Jin Yong HWANG
;
Il Seok CHEON
;
Yu Pan LEE
- Publication Type:Original Article
- Keywords:
Estrogen;
Endothelium-dependent relaxation;
Vascular tonus;
Spontaneously hypertensive rat
- MeSH:
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid;
Acetylcholine;
Angiotensin II;
Animals;
Aorta, Thoracic;
Area Under Curve;
Baths;
Blood Pressure;
Endothelin-1;
Estrogen Replacement Therapy*;
Estrogens*;
Female;
Models, Animal;
Mortality;
Norepinephrine;
Ovariectomy;
Radioimmunoassay;
Rats;
Rats, Inbred SHR*;
Relaxation
- From:Korean Circulation Journal
2000;30(4):528-528
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Although postmenopausal estrogen replacement therapy is known to reduce cardiovascular mortality, the mechanism is not clear yet. Furthermore, the effect of estrogen on vascular tonus is reportedly variable according to the animal models, vascular beds and agonists used. MATERIALS AND METHOD: Bilateral ovariectomies were performed in 12 week-old, 18 spontaneously hypertensive rats (SHR) and 18 normotensive Wistar-Kyoto rats (WKY). Rats were divided into three groups according to the dose of 17beta-estradiol (E 2 ) pellets implanted subcutaneously two weeks after ovariectomy: control (no implantation), low-dose (0.5 mg) and high-dose (5 mg) E 2 replacement group. Two weeks after pellet implantation, organ bath experiments were performed using descending thoracic aortae. For endothelium-dependent relaxation, acetylcholine (10(-9) -3x10(-6) M) was cumulatively added into the vessels precontracted with 10(-7) M norepinephrine (NE). For vasoconstrictor responses, cumulative concentration-contraction curves were constructed in quiescent vessels using NE (10(-9) -10(-5) M), U46619 (10(-9) -3x10(-6) M), endothelin-1 (10(-10) -10(-7) M). In addition, contraction to angiotensin II (10(-7) M) was also obtained. Serum 17beta-estradiol levels were measured by radioimmunoassay. Blood pressure was measured by tail-cuff method in some SHRs before ovariectomy and after placebo/E 2 replacement. RESULTS: Endothelium-dependent relaxation to acetylcholine was impaired in WKY treated with 5 mg E 2 (pIC 50 : control vs 5mg E 2 : 7.75+/-0.13 vs 7.27+/-0.16: n=6: p<0.05). No significant effect was noted in SHR. Contraction to angiotensin II was inhibited by low-dose E 2 in WKY and high-dose E 2 in SHR (% of the contraction to 60 mM KCl: WKY: control vs 0.5 mg E 2 : 39+/-5 vs 25+/-2: SHR: control vs 5 mg E 2 : 34+/-4 vs 22+/-2: n=6 and p<0.05 in WKY and SHR). In contrast, NE-induced contraction was enhanced by E 2 replacement (both low- and high-dose) in WKY and SHR (WKY: control vs 0.5 mg E 2 vs 5 mg E 2 : AUC: 280+/-24 vs 387+/-26 vs 374+/-25: maximal contraction: 137+/-8 vs 166+/-8 vs 162+/-3: pD 2 : 7.63+/-0.11 vs 8.17+/-0.13 vs 8.13+/-0.13: SHR: control vs 0.5 mg E 2 vs 5 mg E 2 : AUC: 265+/-17 vs 349+/-16 vs 406+/-19: maximal contraction: 152+/-6 vs 181+/-9 vs 203+/-16: pD 2 : 7.45+/-0.13 vs 7.91+/-0.08 vs 8.04+/-0.04: n=6 and p<0.05 between control and treated groups in WKY and SHR for all parameters). Contraction to U46619 was enhanced by E 2 replacement in SHR (control vs 0.5 mg E 2 : AUC: 478+/-30 vs 574+/-23: maximal contraction: 181+/-9 vs 230+/-10: n=6: p<0.05 for both parameters). Maximal contractile response to endothelin-1 was also enhanced in SHR (control vs 0.5 mg E 2 vs 5 mg E 2 : maximal contraction: 165+/-7 vs 189+/-7 vs 199+/-8: n=6 and p<0.05 between control and treated groups) but not in WKY. Blood pressure was not different between placebo and E 2- treated SHR (171+/-2 vs 174+/-4 mmHg). CONCLUSION: In WKY, chronic high-dose estrogen replacement impairs endothelium-dependent relaxation to acetylcholine.: low-dose estrogen replacement does not affect endothelium-dependent relaxation in SHR and WKY. Estrogen replacement enhances the contraction to most of the contractile agonists tested except angiotensin II in both WKY and SHR. These results suggest that estrogen replacement affect the vascular tonus differently according to the vasoactive substances and/or hormones without significant effect on blood pressure.
