Maternal High-Salt Intake During Pregnancy Reprogrammed Renin–Angiotensin System-Mediated Cardiomyocyte Apoptosis in the Adult Offspring Heart

1. We investigated the effects of Na+ intake, the renin-angiotensin-aldosterone system and antidiuretic hormone (ADH) on K+ balance during 3 days of frusemide administration to six normal subjects. Subjects received 40 mg of frusemide for 3 days during three different protocols: Na+ intake 270 mmol/day (high salt); Na+ intake 20 mmol/day to stimulate the renin-angiotensin-aldosterone system (low salt); Na+ intake 270 mmol/day plus captopril (25 mg/6 h) to prevent activation of the renin-angiotensin-aldosterone system. In a fourth protocol, a water load was given during high salt intake to prevent ADH release and then frusemide was given. 2. During high salt intake, frusemide increased K+ excretion (UKV) over 3 h, but the loss was counterbalanced by subsequent renal K+ retention so that daily K+ balance was neutral. 3. During low salt intake, the magnitude of the acute kaliuresis following the first dose of frusemide and the slope of the linear relationship between UKV and the log of frusemide excretion were increased compared with that found during the high salt intake. In addition, low salt intake abolished the compensatory renal retention of K+ after frusemide and cumulative K+ balance over 3 days of diuretic administration was uniformly negative (−86 ± 7 mmol/3 days; P < 0.001). 4. Captopril abolished the rise in plasma aldosterone concentration induced by frusemide. The acute kaliuresis after frusemide was unchanged compared with that observed during high salt intake. The compensatory reduction in UKV occurring after the diuretic was slightly potentiated. In fact, captopril given without the diuretic induced a small positive K+ balance. 5. When a water load was given concurrently with frusemide, the acute kaliuresis was >30% lower compared with that seen with frusemide alone, even though the natriuretic response was unchanged. 6. We conclude that: (a) K+ balance is maintained when frusemide is given during liberal Na+ intake because acute K+ losses are offset by subsequent renal K+ retention; (b) this compensatory K+ retention can be inhibited by aldosterone release which could account for the negative K+ balance seen during salt restriction; (c) the short-term kaliuretic response to frusemide is augmented by release of both ADH and aldosterone whereas changes in K+ balance over 3 days of frusemide are dependent on plasma aldosterone concentration.

Download Full-text

Compensatory response to hemorrhage in conscious dogs on normal and low salt intake

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1983.244.3.h351 ◽

1983 ◽

Vol 244 (3) ◽

pp. H351-H356 ◽

Cited By ~ 1

Author(s):

R. I. Kopelman ◽

V. J. Dzau ◽

S. Shimabukuro ◽

A. C. Barger

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Salt Intake ◽

Renin Angiotensin System ◽

Conscious Dogs ◽

Converting Enzyme ◽

Compensatory Response ◽

Angiotensin System ◽

Renin Angiotensin ◽

Low Salt

The compensatory response to moderately severe hemorrhage (30 ml/kg) was studied in chronically catheterized conscious dogs maintained on normal and low salt intake. Although the fall in blood pressure and the increase in heart rate were similar in the two salt states, the salt-restricted animals had significantly greater rises in plasma renin activity and plasma catecholamines following hemorrhage than did the normal salt dogs. To compare further the relative roles of the alpha-adrenergic system and the renin-angiotensin system in the maintenance of blood pressure following hemorrhage, pharmacologic blockade with either phentolamine or converting enzyme inhibitor was performed 20 min after the completion of the hemorrhage. These latter experiments demonstrated that salt restriction resulted in a significantly greater role for the renin-angiotensin system. Moreover, interruption of the renin-angiotensin system blunted the anticipated rise in catecholamines and heart rate during the additional hypotension induced by converting enzyme blockade after hemorrhage.

Download Full-text

Prenatal Exposure to Inflammation Induced by Zymosan Results in Activation of Intrarenal Renin-Angiotensin System in Adult Offspring Rats

Inflammation ◽

10.1007/s10753-010-9199-y ◽

2010 ◽

Vol 33 (6) ◽

pp. 408-414 ◽

Cited By ~ 7

Author(s):

Xue-Qin Hao ◽

Hai-Gang Zhang ◽

Shu-Hui Li ◽

Yi Jia ◽

Ya Liu ◽

...

Keyword(s):

Prenatal Exposure ◽

Renin Angiotensin System ◽

Adult Offspring ◽

Angiotensin System ◽

Renin Angiotensin

Download Full-text

Enhanced intrarenal receptor-mediated prorenin activation in chronic progressive anti-thymocyte serum nephritis rats on high salt intake

AJP Renal Physiology ◽

10.1152/ajprenal.00275.2011 ◽

2012 ◽

Vol 303 (1) ◽

pp. F130-F138 ◽

Cited By ~ 19

Author(s):

Yanjie Huang ◽

Tatsuo Yamamoto ◽

Taro Misaki ◽

Hiroyuki Suzuki ◽

Akashi Togawa ◽

...

Keyword(s):

Apical Membrane ◽

Salt Intake ◽

Kidney Injury ◽

Renin Angiotensin System ◽

Plasma Renin ◽

High Salt ◽

Ang Ii ◽

Kidney Fibrosis ◽

High Salt Intake ◽

Collecting Ducts

Despite suppression of the circulating renin-angiotensin system (RAS), high salt intake (HSI) aggravates kidney injury in chronic kidney disease. To elucidate the effect of HSI on intrarenal RAS, we investigated the levels of intrarenal prorenin, renin, (pro)renin receptor (PRR), receptor-mediated prorenin activation, and ANG II in chronic anti-thymocyte serum (ATS) nephritic rats on HSI. Kidney fibrosis grew more severe in the nephritic rats on HSI than normal salt intake. Despite suppression of plasma renin and ANG II, marked increases in tubular prorenin and renin proteins without concomitant rises in renin mRNA, non-proteolytically activated prorenin, and ANG II were noted in the nephritic rats on HSI. Redistribution of PRR from the cytoplasm to the apical membrane, along with elevated non-proteolytically activated prorenin and ANG II, was observed in the collecting ducts and connecting tubules in the nephritic rats on HSI. Olmesartan decreased cortical prorenin, non-proteolytically activated prorenin and ANG II, and apical membranous PRR in the collecting ducts and connecting tubules, and attenuated the renal lesions. Cell surface trafficking of PRR was enhanced by ANG II and was suppressed by olmesartan in Madin-Darby canine kidney cells. These data suggest the involvement of the ANG II-dependent increase in apical membrane PRR in the augmentation of intrarenal binding of prorenin and renin, followed by nonproteolytic activation of prorenin, enhancement of renin catalytic activity, ANG II generation, and progression of kidney fibrosis in the nephritic rat kidneys on HSI. The origin of the increased tubular prorenin and renin remains to be clarified. Further studies measuring the urinary prorenin and renin are needed.

Download Full-text