Rafael Garcia Robles

Hyperinsulinemia as a determinant of microalbuminuria in essential hypertension.

Objective To analyze the relationship between insulinemia and urinary albumin excretion in a group of nonobese, young adult hypertensive patients, who had never been treated with antihypertensive drugs. Patients and methods Forty-nine patients who fulfilled the inclusion criteria were included. Twenty-four-hour ambulatory blood pressure monitorings, urinary albumin excretion (UAE) measurements, and an oral glucose- tolerance test measuring glucose and insulin, were performed, and left ventricular mass was measured by echocardiography. Hypertensive patients were classified as normoalbuminuric when their UAE was < 30 mg/24 h (40 patients; mean UAE 13.4 ± 7.0 mg/24 h), and as microalbuminuric when their UAE was 30–300 mg/24 h (nine patients; mean UAE 90.5 ± 86.6 mg/24 h). Results In comparison with that of the normoalbuminuric group, the fasting plasma glucose concentration for the microalbuminuric group was only slightly higher (100 ± 9 versus 95 ± 8 mg/dl, NS). In contrast, the fasting insulin concentration in the microalbuminuric group was significantly higher than that observed in the normoalbuminuric group (25.2 ± 6.7 versus 16.6 ± 5.2 µU/ml, P < 0.0001). During the oral glucose-tolerance test, the area under the curve (AUC) for glucose (317 ± 41 versus 253 ± 53 mg/dl x 2/h, P < 0.001) and the AUC for insulin (253 ± 171 versus 124 ± 43 µU/ml x 2/h, P < 0.001) were significantly higher in the microalbuminuric group than were those AUC observed in the normoalbuminuric group. After adjustments for age, sex, body mass index and average 24 h ambulatory mean blood pressure were made, the fasting insulin level was associated independently with an increase in UAE in a multiple regression model with base 10 logarithm of the UAE as the dependent variable. Variations in fasting insulin level alone accounted for 33% of the UAE variance. In contrast, the 24 h ambulatory mean blood pressure, rather than the insulin level, was the strongest predictor of the left ventricular mass index. Conclusions Mild hypertensive patients with microalbuminuria were hyperinsulinemic in the absence of obesity, and their insulin level was the main determinant of microalbuminuria in these patients. Microalbuminuria in essential hypertension seems to identify patients with a cluster of cardiovascular risk factors and a bad risk profile. Thus, assessment of microalbuminuria may be useful in the stratification of risk in essential hypertension.

Salt sensitivity: Concept and pathogenesis

Almost two decades ago, the existence of a subset of essential hypertensive patients, who were sensitive (according to the increase in blood pressure levels) to the intake of a diet with a high salt content, was described. These patients are characterized by an increase in blood pressure and in body weight when switched from a low to a high sodium intake. The increase in body weight is due to the incapacity of the kidneys to excrete the whole intake of sodium until renal perfusion pressure (mean blood pressure) attains a level that is able to restore pressure-natriuresis relationship to values that enable the kidney to excrete the salt ingested or administered intravenously. Salt sensitivity does not seem to depend on the existence of an intrinsic renal defect to handle sodium, but on the existence of subtle abnormalities in the regulation of the sympathetic nervous system, the renin-angiotensin system or endothelial function. It is also relevant that organ damage secondary to arterial hypertension, has been shown in animal models and in hypertensive humans sensitive to a high salt intake to be significantly higher when compared with that of salt-resistant animals or humans. Interestingly, in humans, salt sensitivity has been shown to correlate with microalbuminuria, an important predictor of cardiovascular morbidity and mortality, which correlates with most of the cardiovascular risk factors commonly associated with arterial hypertension. One of these factors is insulin resistance, that usually accompanies high blood pressure in overweight and obese hypertensives. Insulin resistance and hyperinsulinism are present in a significant percentage of hypertensive patients developing cardiovascular symptoms or death. For these reasons, therapy of arterial hypertension must be directed, not only to facilitate the lowering of BP level, but also, to halt the mechanisms underlying the increase in BP, when salt intake is increased. Furthermore, therapy must preferably improve the diminished insulin sensitivity present in salt-sensitive subjects that contribute independently to increased cardiovascular risk.

Prevalence, awareness, treatment and control of hypertension in a Canarian population. Relationship with glucose tolerance categories. The Guía Study.

Objective To estimate the prevalence, awareness, treatment and control of hypertension in a Canarian population; and their relationship with the glucose tolerance categories. Design From a population of 6355 subjects over 29 years old, 690 were chosen in a random sampling. Blood pressure measurements, a standard oral glucose tolerance test (excluding known diabetic patients), and a questionnaire on diabetes and hypertension history and medication use was performed. Results The total prevalence of hypertension was 50.3%; 62.0% of the hypertensive subjects were aware of their condition; 60.6% had their diastolic and 11.0% their systolic blood pressure controlled and 8.6% had both. For diabetic, glucose intolerant and normoglycemic subjects, the respective prevalences of hypertension were 79.4, 60.2 and 43.1% (higher in diabetic subjects, P < 0.001); the awareness of hypertension was 66.7, 61.8 and 59.5% (differences not significant); systolic blood pressure control was 4.8, 14.7 and 13.7% (lower in diabetic subjects, P = 0.017 versus glucose intolerant and P = 0.011 versus normoglycemic subjects); diastolic blood pressure control was 50.4, 72.1 and 63.2% (lower in diabetic subjects, P = 0.004 versus glucose intolerant and P = 0.025 versus normoglycemic subjects). There were no differences in the number and type of antihypertensive drugs among the different glucose tolerance categories. Conclusions Blood pressure was comparable in our population and in other European populations. The prevalence of hypertension was higher, the awareness was similar, and control was worse in diabetic than in non-diabetic subjects; the drug treatment pattern was not different.

Renal effects of fenoldopam in refractory hypertension

Fenoldopam, a dopamine-1 (D1) agonist, was administered by a 6-h intravenous infusion to patients with refractory hypertension [diastolic blood pressure (DBP) greater than 115 mmHg while on triple therapy] in order to achieve a fall in DBP of 30 mmHg. The evolution of blood pressure, heart rate, glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, renal excretion of sodium, potassium, chloride, calcium, uric acid, phosphate, plasma renin activity (PRA), aldosterone and prolactin were evaluated. A significant fall in blood pressure (P less than 0.01) accompanied by an increase in heart rate (P less than 0.01) was attained after 30 min. GFR and RPF increased significantly (P less than 0.01) but the filtration fraction fell. Urine volume and urinary output of sodium, potassium, chloride, calcium, uric acid and phosphate increased markedly (P less than 0.01). Meanwhile, plasma potassium fell (P less than 0.01) and the hormonal parameters showed no significant change. We concluded that in refractory hypertension fenoldopam has potent renal and systemic vasodilatory properties through which blood pressure falls. The hypotensive effect of fenoldopam is also facilitated by its marked diuretic and natriuretic properties. The absence of variations of plasma prolactin confirm the D1 selectivity of fenoldopam and the lack of increase in PRA indicates that fenoldopam blocks the renin-angiotensin-aldosterone system.

Natriuretic effects of dopamine agonist drugs in models of reduced renal mass.

In addition to recognized neurotransmitter properties in the central nervous system, dopamine (DA) plays a role in the physiological activity of the kidney through its hemodynamic and natriuretic effects. On the basis of these data, some pharmacological interventions have focused their attention on the use of DA-related drugs to improve renal sodium handling. We summarize the data obtained from two studies using two DA agonist drugs, lisuride (LIS) and fenoldopam (FEN), in two situations of reduced renal mass. During an intravenous sodium load performed on 10 uninephrectomized dogs, LIS induced a significant blockade of the concomitant pressor response, estimated by lower blood pressure and norepinephrine levels. Under these same conditions, FEN significantly decreased blood pressure and elevated the natriuretic response. In a second study, when FEN was administered at nonhypotensive doses to chronic renal failure patients, it evoked an enhancement of diuresis, natriuresis, and creatinine clearance. These data seem to confirm the involvement of DA in the regulation of cardiovascular homeostasis and its role in renal sodium handling. Furthermore, these beneficial effects support the use of DA-related drugs in the field of hypertension.