Central and peripheral mechanisms of the enhanced hypertension following long-term salt loading in spontaneously hypertensive rats.
We evaluated whether or not increased sodium (Na) concentrations of cerebrospinal fluid (CSF) and stimulated activities of brain renin-angiotensin system (RAS) contribute to an enhanced hypertension by salt overload in spontaneously hypertensive rats (SHR). Long-term salt loading (1% NaCl solution as drinking fluid) accelerated the development of hypertension in SHR, but did not alter the blood pressure (BP) in normotensive Wistar-Kyoto rats (WKY). CSF Na concentration was elevated in uninephrectomized (Nx) group as compared to that in control SHR, while in WKY CSF Na was not influenced by the treatment. A fall in BP by intravenous AVP antagonist or hexamethonium was greater in salt-loaded SHR than in controls. This hypotensive response to the combined blockade of AVP and SNS correlated with CSF Na in SHR but not in WKY. Plasma concentration of AVP and epinephrine tended to increase in relation to the degree of salt loading in SHR but not in WKY. Pressor responses to intracerebroventricular (ICV) angiotensin II (AII) and NaCl were greater in SHR than in WKY, although these responses were not influenced by chronic salt load in either SHR or WKY. The enhanced hypertensive action of ICV NaCl in SHR was abolished by pretreatment with ICV AII antagonist. Chronic saline drinking enhanced the depressor effect of ICV captopril in SHR but not in WKY. These observations suggest that salt overload in SHR may cause an elevated CSF Na concentration and an enhanced activity of brain RAS, which may increase activity of SNS and release of AVP, resulting in an enhanced development of hypertension.
Takata
Y
Y
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka City, Japan.
Yamashita
Y
Y
Takishita
S
S
Tsuchihashi
T
T
Tomita
Y
Y
Kimura
Y
Y
Koga
T
T
Fujishima
M
M
D000818:Animals; D001794:Blood Pressure; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System; D012964:Sodium / Q000134:cerebrospinal fluid; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014667:Vasopressins / Q000378:metabolism / Q000502:physiology
D014667:Vasopressins; D012965:Sodium Chloride; D012964:Sodium