The response was specific for BK, Since Ang-( l-7) did not augment the vasoddatlon induced by elther acetylchohne (0 05 pmol/L) or sodium mtroprusside (0 1 pmol/L) Moreover, neither angiotensm
In pursuit of the hypothesis that estrogen shifts the vasoconstrictor-vasodilator balance of the renin-angiotensin system, we investigated the cardiovascular responses to administration of angiotensin-(1—7) [ANG-(1—7)] and angiotensin II (ANG II) in female transgenic (mRen2)27-positive [Tg(+)] and -negative [Tg(−)] rats in the presence and absence of 3 wk of estrogen replacement therapy. Fifty-three female Tg(−) and Tg(+) rats were oophorectomized and received either 17β-estradiol (1.5 mg/rat sc for 3 wk) or vehicle. At the end of 3 wk of estrogen treatment, mean blood pressure was lowered in freely moving chronically cannulated Tg(+) (159 ± 4 vs. 145 ± 5 mmHg, P < 0.05) and Tg(−) (119 ± 4 vs. 108 ± 2 mmHg, P < 0.05) rats. Moreover, the magnitude of the depressor component of the biphasic response to ANG-(1—7) was significantly enhanced in estrogen-treated Tg(+) rats, whereas the pressor component to ANG-(1—7) was attenuated in both Tg(+) and Tg(−) rats. Estrogen replacement significantly attenuated the pressor response to ANG II in both Tg(+) and Tg(−) rats. In addition, estrogen replacement therapy significantly reduced plasma ANG-converting enzyme activity in association with a reduction in circulating levels of ANG II. Tissue levels (kidney and aorta) of ANG-converting enzyme were also reduced with chronic estrogen replacement therapy. On the other hand, estrogen augmented the levels of plasma ANG-(1—7) in Tg(+) animals. Plasma renin activity was unchanged with estrogen treatment. These findings provide the first evidence demonstrating that estrogen is protective against hypertension, possibly by amplifying the vasodilator contributions of ANG-(1—7), while reducing the formation and vasoconstrictor actions of ANG II.
We have previously demonstrated that mRen-2 transgenic [Tg(+)] rats show a salt-induced exacerbation of hypertension (Callaha, M., P. Li, C. M. Ferrario, D. Ganten, and M. Morris. Hypertension Dallas 27: 573-577, 1996). In this study, we examined the role of paraventricular (PVN) angiotensin type-1 (AT1) receptors in the salt sensitivity of this model. Male Tg(+) and Tg(-) rats were instrumented with PVN cannulas for intracerebral drug administration and carotid catheters for chronic cardiovascular monitoring. Substitution of 2% NaCl for drinking water for 4 days caused a significant elevation (23 mmHg) of mean arterial pressure (MAP) in Tg(+) rats but not in Tg(-) rats. PVN injection of AT1 receptor antisense oligodeoxynucleotides (ASODN), but not scrambled oligodeoxynucleotides (SCODN), produced a rapid decrease in MAP of 24 +/_ 8 mmHg in salt-treated Tg(+) rats. There was no effect of either AT1 ASODN or SCODN on MAP in salt-loaded Tg(-) rats or in Tg(+) rats consuming tap water. Salt loading significantly increased subfornical organ AT1 receptors in Tg(+) rats with no changes produced by ASODN or SCODN. In contrast, there was a 40% decrease in PVN AT1 receptors 20 h after direct PVN injection of AT1 ASODN injection, compared with SCODN in Tg(+) rats. We conclude that PVN AT1 receptors are critical in the expression of salt sensitivity in mRen-2 transgenic rats.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.