Maternal environment alters renal response to angiotensin II in the spontaneously hypertensive rat.
1. The level of hypertension displayed by the adult spontaneously hypertensive rat (SHR) may be reduced by 20-30 mmHg if SHR pups are cross-fostered to a normotensive dam at birth (SHRX). The mechanisms involved are largely unknown, but may involve the kidney and the renin-angiotensin system (RAS) because renal responses to angiotensin (Ang) II are enhanced in the SHR and brief blockade of the RAS in the young rat permanently lowers blood pressure in the SHR. Accordingly, the aim of the present study was to investigate the effect of cross-fostering on the renal response to AngII in the SHR. 2. Renal function was studied in anaesthetized 4-week-old SHR, cross-fostered SHRX and control Wistar-Kyoto (WKY) rats. Standard clearance methods were used to investigate the renal haemodynamic and tubular effects of AngII. The nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was coinfused in some experiments to abolish the counterbalancing effect of nitric oxide. 3. Angiotensin II induced a fall in glomerular filtration rate (GFR) in both SHR and SHRX, but not in WKY rats. This was accompanied by a significant reduction in sodium excretion by SHR but not SHRX pups. This effect appeared to be tubular in origin, because sodium clearance was comparable between the two strains after AngII, but fractional sodium excretion was significantly higher in the SHRX. Coinfusion of the NOS inhibitor L-NAME had little further effect on sodium excretion in SHR and SHRX, but restored GFR in SHRX to levels comparable with those in WKY rats. 4. These data suggest that renal tubular sensitivity to AngII in the SHR can be altered during the early stages of postnatal development, which may contribute to the blood pressure- lowering effect of cross-fostering in the SHR.
Gouldsborough
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I
School of Biological Sciences, University of Manchester, G.38 Stopford Building, Manchester M13 9PT, United Kingdom.
Ashton
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N
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004435:Eating; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008425:Maternal Behavior; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D004791:Enzyme Inhibitors; D000804:Angiotensin II; D019335:Nitroarginine; D019001:Nitric Oxide Synthase