Defective suppression of the aldosterone biosynthesis during stroke permissive diet in the stroke-prone phenotype of the spontaneously hypertensive rat

Previous studies have shown that short-term high salt intake unmasks blunte d plasma aldosterone suppression in stroke-prone spontaneously hypertensive rats (SHRsp). The aim of this study was to evaluate the response of aldost erone biosynthesis and production to a sustained exposure to the stroke-per missive Japanese-style diet (JD) in young stroke-prone and stroke-resistant SHRs. For this purpose, 6-week old male rats from both strains were divide d into 2 dietary groups and received regular diet (SHR = 37, SHRsp = 32) or the JD and 1 % saline to drink (SHR = 34, SHRsp = 30) for 4 weeks. All mea surements were carried out at the end of the dietary periods. After JD, pla sma aldosterone levels were significantly decreased in SHR (from 357.8 +/- 57 to 163.3 +/- 31.5 pg/ml, p < 0.05) but markedly increased in SHRsp (from 442 +/- 56.5 to 739 +/- 125.7 pg/ml, p < 0.05). Consistently, the adrenal aldosterone synthase expression was reduced by JD in SHR (p < 0.05), wherea s it was even slightly raised by JD in SHRsp so that, at the end of JD, ald osterone synthase mRNA was 5-fold higher in SHRsp than in SHR. Urinary sodi um excretion (mEq/24h) achieved lower levels in SHRsp, so that fractional e xcretion of sodium was 80.2 +/- 9 % in SHR and 40.3 +/- 8 % in SHRsp (p < 0 .05) in balance studies performed at the end of JD. These different respons es of mineralocorticoid biosynthesis and urinary sodium excretion to JD wer e not accounted for by different adaptations of the renin-angiotensin and a trial natriuretic peptide systems, of serum potassium levels, or of adrenal 11 beta-hydroxylase expression in the two strains. Systolic blood pressure was comparable in both strains throughout the experiment. These results de monstrate enhanced aldosterone biosynthesis, associated with reduced urinar y excretion of sodium in response to JD in SHRsp before the onset of stroke . This abnormality may play a role in the higher susceptibility to stroke o f this model.