Role of anterior hypothalamic angiotensin II in the pathogenesis of salt sensitive hypertension in the spontaneously hypertensive rat.
Selective alterations in noradrenergic mechanisms in the anterior hypothalamic area (AHA) of NaCl-sensitive spontaneously hypertensive rats (SHR-S) have been demonstrated during dietary NaCl supplementation. To test the hypothesis that endogenous angiotensin II (Ang II) in the AHA also plays a role in blood pressure regulation and in NaCl sensitive hypertension in the SHR-S, Type 1 Ang II (AT1) receptors in the AHA were blocked by local microinjection of losartan, a selective nonpeptide AT1 receptor antagonist, and the effects of the intervention on blood pressure were observed. Microinjection of losartan into the AHA of conscious rats caused a significant dose-related decrease in mean arterial pressure in SHR-S but not in Wistar-Kyoto (WKY) rats. To test the hypothesis that the depressor response to AHA AT1 receptor blockade is enhanced by high (8%) NaCl feeding in SHR-S, losartan was microinjected into the AHA of conscious SHR-S and WKY rats that had been fed 1% or 8% NaCl diets for 3 weeks. The magnitude and duration of the depressor response to losartan were significantly greater in the 8% NaCl fed SHR-S than in the 1% NaCl fed rats. These findings, along with the observation that Ang II receptor numbers are increased in neurons isolated from brain of SHR compared with WKY rats, suggest that endogenous Ang II acting on AT1 receptors in the AHA participates in the tonic control of blood pressure in SHR-S but not in normotensive WKY rats. In addition, it is involved in the pathogenesis of NaCl sensitive hypertension in the SHR-S.
Oparil
S
S
Department of Medicine, University of Alabama at Birmingham 35294.
Yang
R H
RH
Jin
H G
HG
Chen
S J
SJ
Meng
Q C
QC
Berecek
K H
KH
Wyss
J M
JM
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D006973:Hypertension / Q000209:etiology*; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D008845:Microinjections; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D012965:Sodium Chloride; D019808:Losartan