Aldosterone-to-renin ratio depends on age and sex in children attending a clinic for cardiovascular risk assessment.

OBJECTIVE: To determine plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) and aldosterone-to-renin ratio (ARR) values in a population attending a Clinic for Cardiovascular Risk Assessment in Children. METHODS: We assessed ARR and associated factors in a cohort of 287 children (137 female, 4-18 years). Weight and blood pressure (BP) were recorded. PAC (ng/dl) and PRC (mU/l) were measured using direct immunochemiluminescent assays. Data were examined by sex and according to four age classes. RESULTS: Median PAC was similar from the youngest to the oldest age class ranging from 7.5 to 9.9 ng/dl in males and from 11.0 to 12.6 ng/dl in females. Median PRC was also similar across age classes in males ranging from 58.2 to 55.5 mU/l, whereas it progressively decreased from 61.5 to 36.6 mU/l in females (P < 0.01). Median PRC was higher in prepubertal than in pubertal females only (53.6 vs. 40.2 mU/l, P < 0.03). As a result ARR was unchanged with increasing age in males (from 0.18 to 0.19), whereas in females it increased from 0.19 to 0.36 (P < 0.03). After adjusting for body weight, BP and other possible confounders, age was inversely related with PRC and directly with PAC and ARR (P < 0.001 for all), in females only. No relationship was found in both sexes between ARR values, BP, weight and family history of hypertension. CONCLUSION: In our children population, ARR is lower than in adults and diverges with increasing age between sexes, due to the age and puberty driven fall in PRC observed only in females. BP and weight are not associated with ARR distribution.

Stimulation of AT2 receptor exerts beneficial effects in stroke-prone rats: focus on renal damage.

BACKGROUND AND AIM: Angiotensin II acts through two major receptors: AT1-R and AT2-R. It is known that the stimulation of AT1-R mediates vasoconstriction, cell proliferation and fibrosis, aldosterone release and inflammatory response but, although the stimulation of AT2-R is thought to promote vasodilation and anti-inflammatory effects, its real in-vivo functions are still unclear. The aim of this study was to investigate the effects of specific and selective AT2-R stimulation on the pathological events occurring in spontaneously hypertensive stroke-prone rats (SHRSPs). METHODS AND RESULTS: SHRSPs who were fed a high-salt diet underwent long-term treatment with vehicle or compound 21 (C21), a nonpeptide selective AT2-R agonist, at doses of 0.75, 5 and 10 mg/kg per day. The vehicle-treated rats developed brain abnormalities detectable by magnetic resonance imaging after 42.5 +/- 7.5 days, and died 43 +/- 9.5 days after the start of the dietary treatment. The highest C21 dose delayed the occurrence of brain damage (P < 0.001 vs. vehicle-treated SHRSPs) and prolonged survival (P < 0.001) without affecting blood pressure. These beneficial effects of C21 were abolished by the administration of PD123319, an AT2-R antagonist. C21 treatment preserved renal structure by preventing inflammatory cell infiltration, collagen accumulation, and the neo-expression of vimentin; it also prevented the increased plasma renin activity and accumulation of urinary acute-phase proteins observed in the vehicle-treated rats. CONCLUSION: Specific and selective AT2-R stimulation has beneficial effects on the pathological events occurring in SHRSPs. These data indicate a new avenue for the pharmacological treatment of diseases in which modulation of the renin-angiotensin system is required.

Altered release of cytochrome p450 metabolites of arachidonic acid in renovascular disease.

The aim of the present cross-sectional study was to investigate whether activation of the renin-angiotensin system in renovascular disease affects the cytochrome P450 omega/omega-1 hydroxylase (20-hydroxyeicosatetraenoic acid [20-HETE]) and epoxygenase (epoxyeicosatrienoic acids [EETs]) pathways of arachidonic acid metabolism in vivo, each of which interacts with angiotensin II. Plasma concentration and urinary excretion of 20-HETE and EETs and their metabolites, dihydroxyeicosatrienoic acids, were measured in urine and plasma by mass spectrometry in 10 subjects with renovascular disease, 10 with essential hypertension, and 10 healthy normotensive subjects (control subjects), pair-matched for gender and age. Vascular and renal function were evaluated in all of the subjects. Plasma 20-HETE was highest in subjects with renovascular disease (median: 1.20 ng/mL; range: 0.42 to 1.92 ng/mL) compared with subjects with essential hypertension (median: 0.90 ng/mL; range: 0.40 to 2.17 ng/mL) and control subjects (median: 0.45 ng/mL; range: 0.14 to 1.70 ng/mL; P<0.05). Plasma 20-HETE significantly correlated with plasma renin activity in renovascular disease (r(s)=0.67; n=10; P<0.05). The urinary excretion of 20-HETE was significantly lower in subjects with renovascular disease (median: 12.9 microg/g of creatinine; range: 4.4 to 24.9 microg/g of creatinine) than in control subjects (median: 31.0 microg/g of creatinine; range: 11.9 to 102.8 microg/g of creatinine; P<0.01) and essential hypertensive subjects (median: 35.9 microg/g of creatinine; range: 14.0 to 72.5 microg/g of creatinine; P<0.05). Total plasma EETs were lowest, as was the ratio of plasma EETs to plasma dihydroxyeicosatrienoic acids, an index of epoxide hydrolase activity, in renovascular disease (ratio: 2.4; range: 1.2 to 6.1) compared with essential hypertension (ratio: 3.4; range: 1.5 to 5.6) and control subjects (ratio: 6.8; range: 1.4 to 18.8; P<0.01). In conclusion, circulating levels of 20-HETE are increased and those of EETs are decreased in renovascular disease, whereas the urinary excretion of 20-HETE is reduced. Altered cytochrome P450 arachidonic acid metabolism may contribute to the vascular and tubular abnormalities of renovascular disease.

Factors influencing acute ischaemia-induced renal hypertension in rats.

OBJECTIVE: To verify if the acute hypertension that occurs after reversal of complete renal ischaemia is related to the duration of ischaemia, is different in one-kidney (1K) and two-kidney (2K) rats, and is prevented by angiotensin receptor blockade. METHODS: Four groups of Sprague-Dawley rats anaesthetized with pentobarbitone were studied before, during and after a reversible, complete renal ischaemia achieved by functional right nephrectomy. RESULTS: In 1K rats (group 1, n = 21), reopening of right renal hilum after functional right nephrectomy of 180, 60 and 30 min was followed by peak increases in systolic blood pressure of 76.0 10.1 mmHg, 36.5 10.0 mmHg and 18.4 4.4 mmHg, respectively (mean SEM). In 2K rats (group 2, n = 21), functional right nephrectomy of 180, 60 and 30 min was followed by smaller increases in blood pressure of 49.8 7.6 mmHg, 5.9 3.3 mmHg and 8.3 2.1 mmHg, respectively. Plasma renin activity was directly related to the duration of functional right nephrectomy, and was greater in 1K rats. In group 3, irbesartan administered to 1K rats (n = 8) during functional right nephrectomy almost completely prevented the development of hypertension upon reopening. In group 4, labetalol injected intravenously in 1K rats (n = 3) did not prevent the blood pressure surge at reopening (49.2 8.5 mmHg). CONCLUSIONS: An experimental acute renal hypertension may be elicited both in 1K and in 2K rats and for functional right nephrectomy of 30, 60 and 180 min duration. The increase in blood pressure is proportional to the duration of functional right nephrectomy and greater in 1K than in 2K rats. The experimental acute renal hypertension is due to acute release of renin and generation of endogenous angiotensin II, and is specifically prevented by the angiotensin II type 1 receptor blocker, irbesartan, but not by labetalol.