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The relation between basal intrarenal hemodynamics and the renal response to acute inhibition of angiotensin-converting enzyme by captopril and albuminuria was assessed in 106 lean patients with essential hypertension without detectable proteinuria. It was observed that the microalbuminuric group (24.5% of the total population) was characterized by a higher systemic arterial pressure, a lower level of highdensity lipoprotein cholesterol, and similar mean values of age, duration of hypertension, glomerular filtration rate, renal plasma flow, filtration fraction, and plasma renin activity when compared with normoalbuminuric subjects. In response to captopril, a significant renal vasodilatation without a change in M icroalbuminuria (urinary excretion of albumin lower than 200 /xg/min) was proposed as a reliable predictor of the development of overt (proteinuric) nephropathy in patients with insulin-dependent diabetes 1 and of cardiovascular morbidity and mortality in diabetic 2 -3 and nondiabetic 4 populations. The mechanisms and significance of microalbuminuria observed in some patients with essential hypertension are not clearly elucidated because of the lack of simultaneous assessment of the relation between albuminuria and intrarenal hemodynamics and long-term follow-up studies. In the present studies, an attempt was made to evaluate the systemic and renal determinants of microalbuminuria in a population of never-treated patients with mild to moderate hypertension of rather short duration. In addition, the renal response to acute blockade of angiotensin-converting enzyme was assessed to detect contrasting effects in microalbuminuric (MA+) and normoalbuminuric (MA-) patients. Only lean patients were included to eliminate the possible exacerbating influence of overweight in association with high blood pressure on the urinary excretion of albumin. 5 Methods PatientsOne hundred six lean patients (34 women and 72 men) with mild to moderate essential hypertension were included in this study. Age range was 16 to 64 years, and body mass index was lower than 26 kg/m 2 in women and 27 kg/m 2 in men. All subjects had never received antihypertensive medication before participating in the studies. Women on oral contraceptives as well as patients with albustix-positive proteinuria were

We assessed the renal hemodynamic response to L-arginine infusion (30 g within 60 minutes) in normotensive subjects, patients with never-treated essential hypertension, and hypertensive patients controlled by long-term (more than 2 years) treatment with or without an angiotensin-converting enzyme inhibitor. The renal vasodilator response to L-arginine observed in normotensive subjects (15 +/- 4% increase in effective renal plasma flow) was abolished in untreated hypertensive patients and restored only in the group treated by angiotensin-converting enzyme inhibition. In the whole population a positive correlation between the change in effective renal plasma flow and the change in urinary cGMP was obtained. It is suggested that abnormalities of the renal nitric oxide pathway not corrected by increased availability of L-arginine and reversible only on long-term treatment by angiotensin-converting enzyme inhibition may underlie the abnormal renal resistance observed in essential hypertension.

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Genes may modulate the changes of blood pressure (BP) with age; this possibility has never been studied for the age-related increase of pulse pressure (PP), although in older populations, PP is considered the stronger mechanical factor predicting cardiovascular mortality. In humans, the presence of the mutant allele C of the angiotensin II (Ang II) AT 1 -receptor or of the mutant allele T of the eNOS G 298 T gene polymorphisms is associated with enhanced contractile properties of conduit arteries in response to vasoconstrictive agents. In this study, we evaluated, in subjects with untreated essential hypertension, whether the presence of these mutant alleles or their combination might influence the age-related increase of PP. Three main findings emerged from the study and were particularly observed in women: 1) the presence of the C and/or of the T mutant alleles or their combination were associated with a steeper slope of the age versus PP curve, compared with subjects without the mutant allele; 2) the slope was more significantly enhanced when the two mutant alleles were associated in the same genotype; and 3) no comparable age-and gender-related changes in systolic, diastolic or mean BP were found according to this genetic classification. In subjects with essential hypertension, genes may modulate the age-mediated increase of PP. This finding gives new insights in the interactions between genes, mechanical factors and cardiovascular risk. IntroductionIncreased brachial pulse pressure (PP) is an independent predictor of CV risk, mainly for myocardial infarction.1 The value of PP is simultaneously influenced by an increase in systolic blood pressure (SBP) and a decrease of diastolic BP (DBP). In large populations over 50 years of age, cross-sectional and longitudinal studies have shown that cardiovascular (CV) mortality is not only positively correlated to the level of SBP, 2-4 but also that, at any given SBP value, CV mortality is higher when DBP is lower.4 PP is known to be influenced by three main haemodynamic mechanisms: the degree of ventricular ejection, the level of arterial stiffness and the pattern of wave reflections. 5 The two latter, but not ventricular ejection, have been shown to be significant and independent markers of CV risk.