Insulin, renin-aldosterone system and blood pressure in obese people.

OBJECTIVE: To evaluate the relationship between insulin, the renin-aldosterone system and blood pressure in obese subjects. DESIGN AND METHODS: A cross sectional study of a group of severely obese normotensive subjects who were surgical candidates (n=39; mean BMI: 47.8+/-1.4) and a group of hypertensive patients (n=57; mean BMI: 28.0+/-0.7) twenty-nine of whom had BMI>27. All subjects were studied after 15 days on a balanced diet. Insulin, plasma renin activity and aldosterone were measured. RESULTS: Fasting insulin, plasma renin activity and aldosterone were higher in severely obese normotensive subjects than in hypertensive subjects (respectively 32.3+/-3.0 vs 13.1+/-1.0 mU/l, P=0.0001; 1.34+/-0.22 vs 0.88+/-0.12 ng/ml/h, P=0.04; 137.2+/-16.2 vs 87.9+/-12.1 pg/ml, P=0.015). Insulin was related to BMI and to aldosterone both in normotensive and in hypertensive patients. CONCLUSION: Hyperinsulinemia itself does not determine hypertension; in some people it could play a vasodilator role in opposition to the renin-aldosterone system.

Endothelium-derived factors in microalbuminuric and nonmicroalbuminuric essential hypertensives.

Previous evidence has demonstrated a relationship between growth factors and cardiovascular diseases. This study was aimed at evaluating levels of some endothelium-derived growth factors, and their relationship with microalbuminuria (MAU), in essential hypertension. Ninety-nine mild-moderate essential hypertensives (EH) and 25 healthy controls were studied. All patients underwent 24-h blood pressure monitoring, serum endothelin-1 (ET-1), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), and 24-h MAU assays. Later, EH were divided into two subsets consisting of microalbuminurics (MAU >11 microg/min) and nonmicroalbuminurics (MAU <11 microg/min). In microalbuminuric EH, circulating ET-1, bFGF, and PDGF were significantly higher than in nonmicroalbuminurics (P < .0001, P < .0001, P < .005, respectively) or in controls. In the group of 99 EH, significant positive correlations of MAU with both ET-1 and bFGF (r = 0.35, P < .001, and r = 0.34, P < .001, respectively) were found. ET-1 and bFGF correlated significantly (r = 0.31, P < .002). Circulating bFGF also correlated significantly with MAU in the microalbuminuric EH subset (r = 0.49, P < .01). Our results show that in microalbuminuric EH circulating levels of certain growth factors are increased. In human essential hypertension these factors are linked with MAU, an early cardiovascular and renal damage marker.

Sympathetic activity and blood pressure pattern in autosomal dominant polycystic kidney disease hypertensives.

To study the potential role of sympathetic activity in the pathogenesis of arterial hypertension associated with autosomal dominant polycystic kidney disease (ADPKD) and to analyze its relationship with 24-hour blood pressure pattern, plasma catecholamines and 24-hour ambulatory blood pressure monitoring were evaluated in 30 ADPKD hypertensive patients (of which 17 without and 13 with renal failure) and in 50 essential hypertensives. The groups were matched for sex, body mass index, known duration of hypertension, and clinic blood pressure. Plasma catecholamines, determined in resting position, were higher in ADPKD patients without renal failure than in essential hypertensives. Nighttime diastolic blood pressure was higher and the percentage day-night difference in mean blood pressure was lower in hypertensives with ADPKD compared to patients with essential hypertension. Blood pressure was significantly correlated with plasma noradrenaline in ADPKD patients, independently of renal function. No significant differences were observed between ADPKD patients with and without renal failure, with respect to plasma catecholamines, 24-hour daytime and nighttime ambulatory blood pressures and the percentage day-night difference in mean blood pressure.

Microalbuminuria, renal dysfunction and cardiovascular complication in essential hypertension.

OBJECTIVE: To evaluate the prevalence of microalbuminuria (albumin excretion rate, AER) in a wide hypertensive population, and to evaluate any relationship with cardiovascular damage and renal dysfunction. DESIGN: A transversal study. SUBJECTS AND METHODS: In 383 hospitalized Caucasian essential hypertensives (198 men, 185 women) of mean age 44 +/- 0.5 years and mean clinic blood pressure 170.3 +/- 0.95/ 103.4 +/- 0.47 mmHg, metabolic parameters, serum creatinine level (Cs), creatinine clearance rate (Ccs), 24 AER and plasma renin activity (PRA) were measured. Furthermore, each patient underwent 24 h ambulatory blood pressure monitoring (ABPM) and echocardiography to measure left ventricular mass, which was indexed both by body surface area to obtain left ventricular mass index (LVMI) and by height to obtain the left ventricular mass indexed for height (LVMH). By Doppler echocardiography, the diastolic compliance by early:late peak filling velocity ratio was analysed. The fundus oculi was also observed. Three subsets of hypertensives were obtained by dividing the 383 essential hypertensives on the basis of their AER: < or = 11 (group A), 11 < or = 20 (group B) and > 20 micrograms/min (group C). MAIN OUTCOME MEASURES: Microalbuminuria, creatinine clearance, PRA, ABPM, LVMI, LVMH, early:late peak filling velocity ratio, hypertensive retinopathy. RESULTS: Among the 383 essential hypertensives, AER was < 11 micrograms/min in 55% of the patients (group A), 18% had AER in the range 11-20 micrograms/min (group B) and 27% had AER > 20 micrograms/min (group C). In the entire essential hypertensive population the prevalence of left ventricular hypertrophy was 44.39% and hypertensive retinopathy was observed in 54.83%. Moreover, AER significantly correlated with clinic systolic blood pressure (SBP) and diastolic blood pressure (DBP), with 24 SBP and DBP and with 24 h daytime and night-time mean blood pressure (MBP). AER was correlated also with LVMH and creatinine clearance. The analysis of the three subsets revealed no differences in age, body mass index, serum creatinine level and PRA. Group C in comparison with group A showed higher values of clinic SBP, 24 h SBP, DBP and MBP, and of daytime and night-time MBP. Furthermore, in group C, LVMI and LVMH were significantly greater than in group A, with a prevalence of left ventricular hypertrophy of 55% in the former group. Group C showed a prevalence of hypertensive retinopathy of 69% whereas in group A the prevalence was 48%. In group C, AER was significantly correlated with serum creatinine level. CONCLUSIONS: The transversal phase of our research, performed in a homogeneous population of Caucasian essential hypertensives with no metabolic disturbances, confirms the relationship between blood pressure pattern and early glomerular changes in essential hypertensives without overt proteinuria. Furthermore, these results emphasize the role of microalbuminuria as a marker of early cardiac, renal and retinal structural and functional changes in essential hypertension. The longitudinal study, which is in progress, will confirm the prognostic value of microalbuminuria in essential hypertension.

Insulin-like growth factor 1 and pressure load in hypertensive patients.

To verify the effect of a pressure load on the production of Insulin-like Growth Factor 1 (IGF1) in essential hypertensives, we studied 15 patients and 8 normotensive controls before and during orthostatism. Upright standing was characterized both in normals and in hypertensives by significant higher rate-pressure product [RPP = systolic blood pressure (mm Hg) x heart rate (beats/min)]. Proportional increases of RPP were significantly related to IGF1 values at the end of orthostatism and to proportional increases of IGF1 in hypertensive group but not in normotensive one. Our results confirm that IGF1 plasma levels in hypertensive patients are related to pressure load.

The renal functional reserve in recently diagnosed essential hypertension.

Recent studies have shown that both in hypertensives and in offspring of hypertensive parents there exists an altered renal functional reserve (RFR). The aim of this research was to study the RFR in newly diagnosed essential hypertensives, and to evaluate if any influences are played on RFR by circulating renin-angiotensin-aldosterone system, catecholamines, and plasma endothelin-1. In 16 essential hypertensives (EH) and in 10 healthy controls (C), on the 24-hour urine collection and on urine specimens taken after both an oral water load and an amino acids (AAs) infusion (4.16 ml/min for two hours), Ccr, microalbuminuria (AER) and its fractional clearance, and sodium excretion (Nau) were evaluated. Furthermore, both in basal condition and after the AAs load, blood samples were obtained to assay plasma renin activity (PRA) and aldosterone concentrations (PAC), circulating norepinephrine (NE) and endothelin-1 (ET-1). The C-group showed a mean increase in Ccr of 35%. No significant modifications in AER and in circulating hormones were observed. Among the 16 EH, thirteen subjects showed a significant increase in Ccr after the AAs load, with a mean increase of 32.5%. In the whole group of EH there were no significant differences in AER when comparing basal with after-load values, and Nau resulted significantly decreased after AAs infusion. The analysis of the hormonal pattern pointed out not significant changes in the behaviour of PRA, NE and ET-1, while a significant decrease in PAC was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prevalence of microalbuminuria in recent-onset essential hypertension]. / Prevalenza della microalbuminuria nell'ipertensione essenziale di recente insorgenza.

To determine the prevalence of increased microalbuminuria (AER) in essential hypertension, we studied an omogeneous population comprehensive of 160 mild-moderate essential hypertensives (EH) and 30 normotensive controls. All subjects underwent measurement of AER and creatinine clearance (CCl) on the 24-hour urine collection, and of plasma renin activity (PRA). The 24-hour mean arterial pressure (24h-BP) was also obtained by non-invasive ambulatory BP monitoring. The EH were subdivided into subgroups on the basis of their AER values (less or over 11 micrograms/min). Among the 160 EH the prevalence of high AER levels was of 37.5% (n = 60), showing in this subgroup of EH a mean value of 29.5 +/- 4 micrograms/min. Moreover, in the whole population of 160 EH, AER was significantly correlated to 24h-diastolic BP (p < 0.05). The subgroup of 60 EH with AER > 11 micrograms/min showed also Ccl values higher than the other subgroup of EH (p < 0.02), while non significant differences between age, mean duration of EH, PRA, and 24h-BP, both systolic and diastolic, were observed. Our results lead to hypothesize that in essential hypertension there exists a subgroup of subjects characterized, in the early phase of disease, by high capillary glomerular pressure, GFR and microalbuminuria values.

Insulin-like growth factor 1 and sodium-lithium countertransport in essential hypertension and in hypertensive left ventricular hypertrophy.

OBJECTIVE: The aim of this work was to study the insulin-like growth factor 1 (IGF1), a substance able to promote cell proliferation in vascular smooth muscle, in patients with mild-to-moderate hypertension and to analyse its relationship to sodium-lithium countertransport, a genetic marker of hypertension that is related to cardiovascular complications. METHOD: We studied 32 hypertensive subjects, some with left ventricular hypertrophy, and 14 healthy subjects. Fasting plasma IGF1 was measured by means of a radioimmunoassay after octadecylsilica chromatography and Na(+)-Li+ countertransport was determined by the method of Canessa. RESULTS: Hypertensive patients had higher values of both IGF1 and Na(+)-Li+ countertransport. We found a positive correlation, irrespective of age, between IGF1 and Na(+)-Li+ countertransport. The patients with left ventricular hypertrophy had significantly higher plasma IGF1 levels than those without left ventricular hypertrophy. CONCLUSION: Our results confirm a possible role for IGF1 in the cardiovascular complications of hypertension and emphasize its relationship to genetically determined factors.

Screening for congenital renovascular hypoplasia and renal artery stenosis by acute converting enzyme inhibition.

To evaluate the usefulness of the captopril test for identifying renal artery stenosis (RAS) and renovascular hypoplasia (RAH), we studied 48 hypertensive patients. In 20 hypertensives with screening procedures indicating renovascular disease and in 28 essential hypertensives (EH), the plasma renin activity (PRA) responses to an oral test dose of captopril (50 mg) were studied. A 60-min post-captopril PRA increase of 150% (or 400% if baseline PRA < or = 3 ng/ml/h) was considered as positive. Renal angiography was performed in all cases. Among the 20 renovascular hypertensive patients, RAH in 9 and RAS in 11 subjects were proved by angiography. The captopril test in all patients with RAH resulted negative (mean PRA increase 50%); furthermore, the test identified 7 of the 11 RAS (mean PRA increase 477.6%); sensitivity and specificity for RAS were 64 and 88.8%, respectively. In the EH group, there were 3 false-positive subjects (mean PRA increase 122%). This study demonstrates that the PRA responses to a test dose of captopril are a useful screening test for distinguishing RAH from RAS, and for identifying the latter in hypertensive patients. These data also suggest that in subjects with RAH, hypertensive disease may not renin dependent.

Insulin resistance and endogenous digoxin-like factor in obese hypertensive patients with glucose intolerance.

Hypertensive obese subjects with glucose intolerance have hyperinsulinaemia, insulin resistance and intracellular cation imbalance resulting in increased sodium content. The aim of our study was to assess in these patients plasma levels of endogenous digoxin-like factor (EDLF), an inhibitor of the sodium-pump mechanism. We studied 14 hypertensive and 12 normotensive subjects with obesity and glucose intolerance for fasting blood glucose, and plasma insulin, C-peptide and EDLF levels: the two groups were matched for age and BMI and were studied after a 2-week wash-out period from hypotensive drugs. Compared with normotensives, hypertensive subjects had higher plasma insulin levels, a greater immunoreactive insulin/C-peptide ratio, a lower glucose/insulin ratio and higher plasma EDLF levels. Our results confirm that among obese people with glucose intolerance, hypertensives are more hyperinsulinaemic and insulin-resistant than normotensives and indicate that the intracellular cation imbalance in these patients may be attributable, at least in part, to EDLF.

Nifedipine vs. enalapril in treatment of hypertensive patients with glucose intolerance.

To compare the metabolic effects of nifedipine and enalapril, we studied 21 obese patients (BMI of 31.6 +/- 1.1) with mild-to-moderate hypertension and glucose intolerance. None of the patients were receiving insulin or hypoglycemic agents. After a washout period of 15 days, blood pressure was recorded and fasting blood glucose, insulin, and lipid concentrations were determined. At random, 11 patients were started on nifedipine and 10 patients on enalapril. At the 90th day of treatment, clinical and laboratory tests were again performed. Both of the drugs reduced blood pressure values comparably. No significant variation of metabolic parameters was found after 90 days of treatment in the enalapril group. In the nifedipine group, the fasting insulin level was decreased and the glucose/insulin ratio was significantly increased, suggesting an improvement in insulin sensitivity; moreover, total plasma cholesterol was significantly reduced. Enalapril and nifedipine seem to be effective and safe drugs in the treatment of hypertensive subjects with obesity and glucose intolerance. Nifedipine can ameliorate insulin resistance and the lipid state.

[Arterial hypertension caused by low renin: comparison of the calcium antagonist nifedipine and the ACE-inhibitor enalapril as to antihypertensive efficacy]. / Ipertensione arteriosa a bassa renina: comparazione tra il calcio-antagonista nifedipina e l'ACE-inibitore enalapril sulla efficacia antiipertensiva.

The aim of this study was to compare the clinical effects of calcium-entry blocker Nifedipine and ACE-inhibitor Enalapril in hypertensive patients with glucose intolerance that have lower plasma renin activity. A blood sample for basal PRA was obtained from 21 subjects; then, 11 patients received Nifedipine (20 mg. b.i.d.) and 10 Enalapril (20 mg. q.d.). The extent of blood pressure fall after 12 weeks of treatment was inversely related to basal PRA levels in Nifedipine treated group only; however, the hypotensive effect of both drugs was comparable.

[Usefulness of captopril test in diagnosis of renal artery stenosis and congenital small kidney in arterial hypertension]. / Utilità del test al captopril nello screening della stenosi dell'arteria renale e del rene piccolo congenito nell'ipertensione arteriosa.

We studied 45 hypertensive subjects to evaluate the usefulness of captopril test for identifying renal artery stenosis and small congenital kidney with the hypoplasia of the renal artery. In 18 hypertensives with hippuran renogram indicating renovascular disease, and in 27 essential hypertensives, the plasma renin activity (PRA) responses to an oral test dose (50 mg) of captopril were studied. A 60-minute post captopril PRA increase of 150% (or 400% if baseline PRA less than 3 ng/ml/h) was considered as positive. Digital venous angiography was performed in all cases. In the group of 18 subjects small congenital kidney in 7, and renal artery stenosis in 11 subjects were detected by angiography. Captopril test resulted negative in all patients with small congenital kidney (mean PRA% increase 58). The test identified 7 of the 11 renal artery stenoses (mean PRA% increase 477), sensitivity and specificity were 64% and 100% respectively. In the essential hypertensives-group, mean PRA% increase was 122; there were three false positives, and both sensitivity and specificity were 88%. This study demonstrates that the PRA response to oral captopril test is a useful screening test for distinguishing small congenital kidney from renal artery stenosis and for identifying the latter in hypertensive patients.

[Microalbuminuria, an early marker of renal changes in essential hypertension]. / Microalbuminuria, precoce marker delle modificazioni renali nell'ipertensione essenziale.

The purpose of this study was to verify if microalbuminuria (AER) could be an early feature of renal hemodynamic changes in essential hypertension. Fifty-three patients with newly diagnosed essential hypertension (EH) underwent 24-hour blood pressure monitoring (24h-BP). Furthermore, AER and glomerular filtration rate (GFR) were evaluated by obtaining 24-hour urine collection: day- and night-time urine was kept separate. Data from the 53 EH patients were analyzed both collectively and after subdivision into two subgroups based on AER values (less or more than 16 micrograms/min). In the 53 EH patients, 24h-AER correlated significantly to both 24h systolic and diastolic blood pressure (BP) (r = 0.58 and 0.67, respectively). The subgroup with AER greater than 16 micrograms/min showed higher values of 24h-BP and GFR than the other subgroup. Moreover, in the first subgroup, 24h-systolic BP (r = 0.61) and 24h-diastolic BP (r = 0.68) correlated with AER. Our data seem to indicate that among the hypertensive patients, there is a subgroup of subjects whose hypertensive disease is characterized by high blood pressure as well as elevated microalbuminuria and glomerular filtration rate values. Increased microalbuminuria in newly diagnosed hypertensive disease seems to be due to glomerular hypertension and early altered microvascular permselectivity, and would thus indicate an early clinical expression of altered renal hemodynamics.

[Endogenous digoxin-like factor: serum concentration and interrelations with the electrolyte picture in normal subjects]. / Fattore simil-digossinico endogeno: concentrazione sierica ed interrelazioni con il quadro elettrolitico nei soggetti normali.

Endogenous Digitalis-Like Factor (DLF) is a putative hypothalamic Na+,K+-ATPase inhibitor that mediates natriuresis in response to intravascular volume expansion or sodium loading. The precise structure of this substance remains unknown; however, it cross-reacts with antibody to digoxin. Using a radioimmunoassay, we measured DLF concentrations in 26 normal subjects: mean value of this factor was 0.512 ng digoxin-equivalents/ml +/- 0.038 SEM; DLF correlated significantly with serum sodium levels (r = 0.59 - p less than 0.01) and daily urinary sodium excretion (r = 0.48 - p less than 0.05). Our results confirm that endogenous digitalis-like factor has a physiological role as regulator of natriuresis, in response to plasma sodium concentrations.

Treatment of malignant hypertension with an angiotensin converting enzyme inhibitor.

Malignant hypertension developed in an 18-year-old man whose primary hypertension had been diagnosed by chance. Standing blood pressure was 290/170 mmHg. Tests of renal function revealed high blood urea nitrogen and creatinine levels and low levels of both effective renal plasma flow and the glomerular filtration rate. Plasma renin activity and levels of angiotensin II and aldosterone were greatly elevated. Severe concentric left ventricular hypertrophy was noted. The patient received standard antihypertensive treatment with furosemide, propranolol, nifedipine, and prazosin, but his blood pressure did not decrease and there was no improvement in the clinical or biochemical measures. The patient was then given 20 mg of enalapril daily for one year. The inhibition of angiotensin converting enzyme immediately reduced blood pressure. Angiotensin II and aldosterone levels became normal, kidney function and hemodynamics improved, and echocardiograms revealed that the left ventricular hypertrophy had regressed. The results confirm the pathogenetic role of angiotensin II in the development of the malignant phase of hypertension.