[Excess of mineralocorticoids in essential hypertension: clinical-diagnostic approach]. / Exceso de mineralocorticoides en hipertensos esenciales: enfoque clínico-diagnóstico.

BACKGROUND: Primary hyperaldosteronism is more frequent among subjects with essential hypertension than previously thought. The prevalence, according to local and international evidence could fluctuate between 9 and 10%. AIM: To investigate if subjects with essential hypertension have different aldosterone and renin plasma levels than normotensive subjects. PATIENTS AND METHODS: One hundred twenty five subjects with essential hypertension, not receiving medications for at least two weeks prior to the study and 168 age and sex matched normotensive controls were studied. Blood was drawn between 9 and 10 AM during a sodium free diet to determine plasma aldosterone, plasma renin activity and potassium. RESULTS: Plasma aldosterone was higher in hypertensive subjects than controls (11.6 +/- 7.6 and 9.9 +/- 5.1 ng/dl respectively; p = 0.04). Plasma renin activity was lower in hypertensives than controls (1.42 +/- 1.28 and 1.88 +/- 1.39 ng/ml/b respectively; p < 0.001). Thus, plasma aldosterone/plasma renin activity ratio was higher in hypertensives (13.8 +/- 13.5 and 8.3 +/- 7.8; p < 0.001). A pathological ratio was defined as over 25, corresponding to the mean plus two standard deviations of the control group. Primary hyperaldosteronism was found in 5/125 hypertensives (4%) and 1/168 normotensive subject (0.6%). None had hypokalemia. CONCLUSIONS: Subjects with essential hypertension have higher plasma aldosterone and lower plasma renin activity than normal controls. A plasma aldosterone/plasma renin activity over 25 was defined as abnormal.

A(-6)G variant of angiotensinogen gene and aldosterone levels in hypertensives.

Recently, a novel mutation in the promoter region of the angiotensinogen gene that involves the presence of an adenine instead of a guanine 6 bp upstream from the transcription initiation site (A(-6)G) has been shown to induce an increase in gene transcription. The aim of this study was to determine the prevalence of the A(-6)G mutation in essential hypertensive patients and to correlate it with aldosterone and renin activity levels. We studied 191 hypertensives. We measured levels of aldosterone (plasma and urinary) and plasma renin activity. We determined the variants A and G using a mutagenically separated polymerase chain reaction technique. In 191 hypertensives, the A variant was detected in 266 of 382 (69.6%) and the G variant in 116 of 382 alleles (30.4%). Plasma aldosterone was significantly higher in patients homozygous for AA than in those homozygous for GG (369+/-208 versus 246+/-142 pmol/L). Urinary aldosterone was significantly higher in homozygous AA than in AG or GG patients (62.4+/-39.4 versus 50.8+/-25.2 and 37.4+/-22.3 nmol/d, respectively). When the patients were grouped according to the presence or absence of the A allele, the aldosterone levels and the plasma aldosterone/plasma renin activity ratio were significantly higher in patients with the A allele. The presence of the A variant was associated with higher levels of aldosterone. These results suggest that the presence of the A variant could determine the appearance of arterial hypertension through higher transcription activity of the angiotensinogen gene and concomitant aldosterone production.

T235 variant of the angiotensinogen gene and blood pressure in the Chilean population.

BACKGROUND: The angiotensinogen gene has recently been linked to essential hypertension. A variant within this gene, encoding threonine rather than methionine at amino acid position 235, was associated with essential hypertension. However, results of new studies have not confirmed this association, suggesting that ethnic differences may explain the different results. OBJECTIVE: To evaluate whether the T235 variant is associated with a higher incidence of essential hypertension among Hispanics (a group that has scarcely been evaluated) and to determine whether T235 is associated with variations in the plasma renin activity or the serum aldosterone level. PATIENTS AND METHOD: We studied 64 patients with essential hypertension and 62 normotensives, matched for age and sex. We obtained samples for determinations of plasma renin activity, serum aldosterone level and genome DNA from all subjects. The genomic DNA was amplified using the polymerase chain reaction technique and digested by the restriction enzyme streptococcus faecalis (Sfa NI) which cuts M235 only, not T235. RESULTS: The patients with essential hypertension had a higher prevalence of the risk variant T235 (alleles 77/128 = 60.2%) than did the normotensive controls (alleles 65/124 = 52.4%), but the difference was not statistically significant (chi2=1.53, P=0.22). The plasma renin activity levels in hypertensives were not statistically different for homozygous T235, heterozygous and homozygous M235 (1.0 +/- 0.96, 2.0 +/- 2.25 and 1.55 +/- 1.49 ng/ml per h, respectively, P=0.5 1). However, when we considered those hypertensives with low plasma renin activity levels (< 1 ng/ml per h), we found a high prevalence (72.7%) of subjects homozygous for the T235 variant. We found no association between the T235 variant and the serum aldosterone levels in hypertensive and normotensive subjects. CONCLUSIONS: We demonstrated that there is a high prevalence of T235 variant in our Hispanic population. The slight difference between prevalences of T235 variant among hypertensive and normotensive subjects that we found was not statistically significant and did not permit us to establish an association between T235 variant and essential hypertension. We believe that only studying a larger cohort of subjects could show whether there is a quantitative effect of the T allele on plasma renin activity levels.