Role of paraventricular angiotensin AT1 receptors in salt-sensitive hypertension in mRen-2 transgenic rats.
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.
Li
P
P
Department of Physiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA. Pli@mdcenter.wpmail.wfu.edu
Morris
M
M
Diz
D I
DI
Ferrario
C M
CM
Ganten
D
D
Callahan
M F
MF
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D001345:Autoradiography; D001794:Blood Pressure; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D016376:Oligonucleotides, Antisense; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology*
D016376:Oligonucleotides, Antisense; D011945:Receptors, Angiotensin; D012965:Sodium Chloride