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Biomedical subjects

P Weidmann

Publications and source records attributed to P Weidmann.

At least 37 records · Page 2Linked to original sources
PubMed1995

Lisinopril is neutral to insulin sensitivity and serum lipoproteins in essential hypertensive patients.

To investigate the effects of antihypertensive treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril on insulin sensitivity and related metabolic variables, the insulin sensitivity index (SI), determined with the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure were assessed in 24 lean, non-diabetic patients with essential hypertension. Following a double-blind, randomised crossover design, these parameters were measured after a 4-week run-in period, after 8 weeks of lisinopril or placebo, and after an additional 8 weeks on placebo or lisinopril, respectively. Furthermore, the level of physical fitness was estimated using the Conconi bicycle ergometer test. SI was low in this study population (5.6 vs 13.3 x 10(-4).min-1.mU-1.l-1 in normal lean control subjects). It did not differ between the placebo run-in phase, the lisinopril phase, and the placebo crossover phase (5.8, 5.5, and 5.4 x 10(-4).min-1.mU-1.l-1, respectively). Moreover, during the administration of lisinopril, no significant changes occurred in fasting plasma insulin and glucose, areas under the glucose and insulin curves, glucose disappearance rate, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions. Heart rate at rest, body weight, and anaerobic threshold remained stable throughout the study. Compliance assessed by pill-counting exceeded 90% at all visits. These findings demonstrate that the ACE inhibitor lisinopril is neutral with regard to insulin sensitivity, plasma insulin and glucose, and lipoprotein metabolism in patients with essential hypertension.

Adult↗
PubMed1995

Insulin resistance and hyperinsulinemia in hypertension.

GENETIC PREDISPOSITION: Insulin resistance and reactive hyperinsulinemia occur not only with obesity, impaired glucose tolerance or non-insulin-dependent (type 2) diabetes mellitus, but also in many non-obese, non-diabetic patients with essential hypertension and their currently normotensive, lean, young offspring, as well as in some other conditions known to promote hypertension. Insulin resistance impairs glucose tolerance, while insulin resistance and/or hyperinsulinemia promote dyslipidemia, body fat deposition and probably atherogenesis. Therefore, the common coexistence of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent, although temporally often dissociated, occurrence of hypertension together with dyslipidemia, obesity and type 2 diabetes in a given patient. INSULIN RESISTANCE AND HYPERINSULINEMIA AS SLOW PRESSOR MECHANISMS: In the pathogenesis of hypertension, inappropriate vasoconstriction (due to an imbalance of vasoactive substances and/or raised cytosolic calcium) and/or structural vasculopathy is particularly important. Among the mosaic of assumed pressor mechanisms, distinct Na+ retention is almost invariably involved in diabetes mellitus, while sympathetic activation tends to occur in essential hypertension, particularly in association with obesity. Insulin resistance may develop as a consequence of an intracellular excess of Ca2+ or a decrease in Mg2+, an impaired insulin-mediated rise in skeletal muscle blood flow, increased sympathetic activity or excess body weight. Acute hyperinsulinemia causes arterial vasodilation on one hand and increases sympathetic activity and renal Na+ reabsorption on the other. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis, while insulin resistance may be associated with certain transmembraneous cation transporters, leading to an increase in cytosolic Ca2+. Hyperinsulinemia and/or insulin resistance may also be associated with an increased blood pressure sensitivity to high salt intake. In the mosaic of many different blood pressure-raising mechanisms, insulin resistance and/or hyperinsulinemia is likely to represent an amplifying slow or very slow pressor factor.

Coronary Disease↗
PubMed1995

Inhibition of rat glomerular mesangial cell sodium/hydrogen exchange by hydrogen peroxide.

1. pHi regulation in glomerular mesangial cells (GMC) includes both Na+/H+ and Cl-/HCO3-exchange. As a fall in pHi may protect against H2O2-mediated GMC damage during ischaemia-reperfusion, the involvement of these mechanisms in the GMC pH1 response to H2O2 was assessed using confluent GMC grown in RPMI medium with 20% fetal calf serum (10-15 passages). 2. Cells were loaded with BCECF-AM and pH1 evaluated using standard fluorometric-ratio techniques. In HEPES buffer, GMC exposure to H2O2 dose-dependently (25 mumol/L-1 mmol/L) decreased pHi over 10 min from 7.3 +/- 0.1 to 6.7 +/- 0.1 (at 100 mumol/L) partly due to rapid non-competitive inhibition of amiloride-sensitive Na+/H+ exchange. 3. BCECF fluorescence in free solution was unchanged by H2O2 and averaged 100 +/- 9 nmol/2.6 x 10(6) cells/pH unit. Similarly, zero-Na+/high-K+ buffer, used to minimize passive H+ entry, did not prevent the fall in pHi while GMC H+-formation/extrusion, assessed by the rate of extracellular acidification in low-capacity buffer (0.05 mmol/L), was rapidly inhibited. 4. In contrast, following only a brief 3 min exposure to 1 mmol/L H2O2, HCO3-/CO2 buffer potentiated the inhibition of Na+/H+ exchange from 50 to 80% of control and reduced the acidification from pHi 6.6 +/- 0.1 to 7.15 +/- 0.05. This effect was reversed (to pHi 6.8 +/- 0.07) by pretreatment with 200 mumol/L DIDS, an inhibitor of Cl-/HCO3- exchange. 5. Thus, the decrease in GMC pHi in response to H2O2 in HEPES, partly mediated by inhibition of Na+/H+ exchange and a possible redistribution of intracellular H+, is antagonized in HCO3-/CO2 through a DIDS-sensitive Cl-/HCO3- exchange mechanism. This may act to negate potentially protective effects of low pHi and potentiate oxidative damage to membrane lipids, enzymes and intracellular organelles on reperfusion.

Animals↗
PubMed1995

Role of intracellular signalling pathways in hydrogen peroxide-induced injury to rat glomerular mesangial cells.

1. Brief exposure of cultured rat glomerular mesangial cells (GMC) to H2O2 in nominally bicarbonate-free solution induced a rapid dose dependent, dantrolene-inhibitable increase in intracellular free Ca2+ from 65 +/- 6 to 203 +/- 14 nmol/L and a prolonged release of [14C]-arachidonic acid [14C]-AA which preceded the onset of cell membrane damage assessed by trypan-blue uptake. 2. Ca2+ responses were potentiated in HCO3-/CO2 containing buffers and reached values of 1145 +/- 100 nmol/L at 1 mmol/L H2O2. In HCO3-/CO2 solutions, but not HEPES buffer, H2O2-induced Ca2+ increases were markedly attenuated by verapamil (100 mumol/L) or removal of extracellular calcium. 3. Enhanced release of [14C]-AA was partially attenuated by inhibitors of key intracellular signalling mechanisms including the phospholipase-A2 (PLA2) inhibitor mepacrine (100 mumol/L), the NADPH oxidase inhibitor diphenyliodonium (10 mumol/L), the mitochondrial calcium-cycling inhibitor ruthenium red (10 mumol/L) and the iron chelator dipyridyl (100 mumol/L). Release was unaffected by protein kinase C inhibition with H7 (100 mumol/L), inositol triphosphate antagonism with neomycin (1 mmol/L) or overnight treatment with the G-protein antagonist pertussis toxin (5 micrograms/mL). 4. Several structurally diverse lipoxygenase inhibitors, including esculetin, baicalein and phenidone, over the dose range 1-100 mumol/L, also prevented [14C]-AA release and markedly protected against cell membrane damage. No drug directly scavenged H2O2 assessed by UV absorption. 5. These results indicate that H2O2 activates in GMC a complex series of interrelated pathological mechanisms which in turn contribute to a prolongation of oxidative damage beyond the time of the initial exposure. These include an increase in intracellular calcium which, depending upon conditions, appears to be mediated by release from intracellular stores as well as Ca2+ entry from the extracellular space. In turn there is a sustained release of arachidonic acid, which may partly depend on prolonged activation of PLA2 but not phospholipase C. 6. Release of [14C]-AA could be attenuated by inhibitors of NADPH oxidase, mitochondrial calcium-cycling, iron chelators and a structurally diverse range of lipoxygenase inhibitors in association with protection from H2O2-mediated cell membrane damage.

Animals↗
PubMed1995

[Insulin resistance and arterial hypertension].

Insulin resistance and reactive hyperinsulinemia occur not only in patients with obesity, impaired glucose tolerance or non-insulin-dependent (Type 2) diabetes mellitus, but also in many non-obese, non-diabetic individuals with essentiell hypertension and their normotensive, lean young offsprings. The common coexistance of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent occurrence of hypertension as well as dyslipidemia, obesity and diabetes Type 2 in a given individual. In the pathogenesis of hypertension, inappropriate vasoconstriction and/or a structural vasculopathy appears to be an important and ultimate causative event. Several pressor mechanisms are discussed and a distinct sodium retention appears to be almost obligatory associated with diabetes mellitus, while essential and particularly obesity-associated hypertension involves predominantly a tendency for sympathetic activation. Acute hyperinsulinemia on one hand causes arterial vasodilation and on the other hand enhances renal sodium reabsorption and sympathetic activity. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis. Insulin resistance affecting certain transmembrane cation transporters might lead to an elevation of intracellular cytosolic calcium levels thereby inducing inappropriate vasoconstriction. Nevertheless, whether insulin resistance and hyperinsulinemia contribute to the pathogenesis of hypertension per se is still unproven. Considering antihypertensive drugs, thiazide diuretics given in medium or high dosage as well as beta-blockers appear to promote insulin resistance, reactive hyperinsulinemia and dyslipidemia. Almost all calcium antagonists and the conventional sympthatolytics are metabolically neutral, while ACE-inhibitors and alpha 1-blockers tend to improve insulin resistance. In Type 2 diabetic patients, ACE-inhibitors exert in addition to their antihypertensive a potentially useful anti-diabetic effect. Nevertheless, the prognostic relevance of the metabolic side effects of antihypertensive drugs awaits further clarification.

Antihypertensive Agents↗
PubMed1994

Acute sodium loading in patients with uncomplicated diabetes mellitus: renal and hormonal effects.

1. Diabetes mellitus is associated with high body sodium, but the pathogenetic mechanism is still unknown. The possibility that an abnormal renal handling of sodium, an abnormal responsiveness of sodium-modulating factors or a shift in the set point for sodium metabolism may contribute to or be associated with sodium retention was tested with an acute saline infusion. 2. A consecutive sample of 33 patients with stable non-azotaemic diabetes mellitus (24 insulin-dependent patients) and 30 normal control subjects was studied. Two litres of a 0.9% NaCl infusion were infused over 4 h. The urinary sodium excretion during the infusion and the next 18 h was analysed in relation to blood pressure, creatinine and lithium clearances, Na(+)-K+ co-transport, Na(+)-Li+ countertransport, plasma levels of renin, angiotensin II, aldosterone, noradrenaline, adrenaline, atrial natriuretic factor and digoxin-like factor. 3. Diabetic patients and control subjects did not differ in blood pressure, body mass index, clearances of creatinine, sodium or lithium, intracellular sodium Na(+)-K+ co-transport and Na(+)-Li+ countertransport, urinary and plasma levels of digoxin-like factor, plasma renin activity, angiotensin II, aldosterone, noradrenaline, adrenaline and atrial natriuretic factor. The intravenous saline infusion caused a similar natriuresis in diabetic patients and normal subjects; the renin-angiotensin-aldosterone system was suppressed to a higher degree in diabetic patients than in normal subjects, whereas atrial natriuretic factor was stimulated to a similar extent; plasma digoxin-like activity was unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Comparative study of the effect of ACE-inhibitors and other antihypertensive agents on proteinuria in diabetic patients.

Several studies during the past 15 years have shown that antihypertensive therapy with different types of drugs can reduce microalbuminuria or clinical proteinuria and retard the progression toward end-stage renal failure. However, some authors reported disparate renal protective effects of different antihypertensive drugs in diabetic animals and humans. In an attempt to resolve the controversy surrounding this possibility, previously we reported a meta-analysis of published studies in diabetics with microalbuminuria or overt proteinuria treated with conventional agents, angiotensin-converting enzyme (ACE) inhibitors, or calcium antagonists (Ca2+ antagonists). Here we present an updated meta-analysis of published studies in diabetics with microalbuminuria or clinical proteinuria (UProt), treated during > or = 4 weeks with ACE inhibitors, Ca2+ antagonists, or conventional therapy (diuretic and/or beta-blocker). Despite similar blood pressure (BP) reductions, UProt tended to decrease more on ACE inhibitors (on average -45%) than on conventional therapy (on average -23%) or Ca2+ antagonists other than nifedipine (on average -35%); in contrast, UProt tended to increase slightly on nifedipine (on average 5%, P < .05). On the basis of multiple regression analysis, ACE inhibitor-induced UProt changes correlated with BP changes (r = 0.77, P < .00001), averaged -28% at zero BP change, and varied 1.5% for each percent BP change. On conventional therapy, UProt and BP changes also correlated (r = 0.62, P < .005), but UProt began to decrease only after a BP reduction of > 5% and the slope was steeper (4% UProt change per percent BP change) than on ACE inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1994

Insulin sensitivity and atrial natriuretic factor during beta-receptor modulation with celiprolol in normal subjects.

beta-Receptor blockers may exert a spectrum of metabolic and humoral effects, which might differ depending on the specific adrenoreceptor characteristics of the individual agents. We investigated the influence of celiprolol, a beta 1-blocker with beta 2-agonistic and, possibly, additional weak alpha-receptor antagonistic properties, on insulin sensitivity (SI), glucose homeostasis, and lipid profile in 20 young, healthy, normotensive individuals. SI, fasting plasma glucose and insulin, serum total triglycerides (TG), lipoprotein cholesterol (C) fractions, lipoprotein a [Lp(a)], and plasma atrial natriuretic factor (ANF) levels were determined before and after acute glucose loading under placebo conditions and after 3 weeks of celiprolol administration. The participants were instructed to follow a 3-day standard diet (2,500 kcal/day, 45% carbohydrates, 40% fat, and 15% protein) and an overnight fast before measurements were recorded. As compared with control values, SI, fasting plasma glucose and insulin, the areas under the glucose and insulin curves, the k value of glucose disappearance after glucose load, and serum cholesterol fractions, TG, and Lp(a) were unchanged during celiprolol administration. However, celiprolol significantly reduced plasma ANF levels (p < 0.02). The latter increased in response to acute hyperglycemia/hyperinsulinemia with placebo (p < 0.05) but not with celiprolol. Although diastolic blood pressure (DBP) decreased slightly during the first and second week of celiprolol administration, BP and heart rate (HR) did not differ significantly after 3 weeks on celiprolol treatment as compared with placebo conditions. Our findings demonstrate that in healthy lean humans beta-receptor modulation with celiprolol is neutral with regard to SI and lipoprotein metabolism. Moreover, glucose loading stimulates whereas celiprolol decreases plasma ANF levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-1 Receptor Antagonists↗
PubMed1994

Differential effects of antihypertensive drugs on hypertension: associated risk factors.

The primary aim of the management of hypertension should be to prevent coronary heart disease. Antihypertensive treatment should have a beneficial effect on the risk factors associated with coronary heart disease, particularly hypertension, dyslipidemia, hyperinsulinemia, and/or glucose intolerance. Other important risk factors include central obesity, left ventricular hypertrophy, hypokalemia, and smoking. In patients genetically predisposed to essential hypertension, metabolic alterations characterized by insulin resistance, hyperinsulinemia, and dyslipidemia tend to occur already before the development of hypertension, obesity, or redistribution of body fat. In the treatment of normotensive or borderline hypertensive diabetic patients, angiotensin-converting enzyme (ACE) inhibitors have shown superiority to other agents due to their antiproteinuric effect and their beneficial influence on the glomerular filtration rate. ACE inhibitor treatment of patients with overt diabetic nephropathy has been reported to reduce the risk of mortality and the need for dialysis or transplantation. Beta blockers and thiazide diuretics are still the 'gold standard' of antihypertensive therapy in non-diabetic patients, as they offer at least some prognostic benefit, while the influence of the newer antihypertensive drugs on morbidity and mortality in these patients is not yet known. Nevertheless, since practicing physicians have to treat patients rather than statistical numbers, the current trend towards a more individualized selection, including the newer antihypertensive drugs with consideration of their metabolic, cardiac, and renal action profile, is also difficult to rebut. ACE inhibitors and most calcium antagonists have already evolved as the preferred drugs for the treatment of hypertension in diabetics due to their favorable effects on some of the cardiovascular and renal risk factors.

Antihypertensive Agents↗
PubMed1993

[Pravastatin in the treatment of primary hypercholesterolemia: a Swiss multicenter study].

Conventional lipid-lowering agents displayed only limited efficacy in lowering total and LDL cholesterol and a high incidence of side effects. Pravastatin is a new potent cholesterol-lowering agent, which selectively inhibits hepatic HMG-CoA-reductase. In a double-blind, placebo-controlled Swiss multicenter study with determination of lipids and lipoprotein in a central laboratory, the efficacy and safety of 6 months' therapy with pravastatin was evaluated in 50 patients with mild hypercholesterolemia and additional coronary risk factors. Compared to baseline and after 26 weeks' therapy, pravastatin significantly reduced total cholesterol (pravastatin vs placebo, -17% vs +7%, p < 0.0001) and LDL cholesterol (-26 vs +2%, p < 0.0001). The total/HDL cholesterol ratio ( = "atherogenic index") was comparable in the two groups at baseline (5.9 +/- 1.1 vs 6.3 +/- 0.9), and was distinctly lowered by pravastatin but not placebo (-20 vs 0%, p < 0.0001). In 11 patients in whom the reduction of serum total cholesterol after 13 weeks' treatment with 20 mg pravastatin was still below target (on average -9.1%), doubling of the dose produced a further decrease of 4.3%. Serum HDL cholesterol and serum triglyceride levels did not change significantly during pravastatin treatment as compared to baseline and placebo. Pravastatin was well tolerated during the 26 weeks without relevant subjective side-effects. There were 5 dropouts during the study, 2 patients in the pravastatin group and 3 in the placebo group. These findings document that pravastatin, administered in a single daily dose of 20 to 40 mg, effectively lowers serum cholesterol and total-/HDL-cholesterol improving action and is well tolerated.

Cholesterol, HDL↗
PubMed1993

Insulin sensitivity and body fat distribution in normotensive offspring of hypertensive parents.

Lean, healthy normotensive sons of essential hypertensive parents (OHyp) have lower insulin sensitivity (SI) than sons of normotensive parents (ONorm). We have tried to find out whether this disturbance in insulin metabolism is related to altered body fat distribution, fuel metabolism, or both. 21 OHyp and 21 ONorm of similar age and body-mass index were investigated after fasting overnight. Body composition was assessed by dual-energy X-ray absorptiometry and fuel metabolism by indirect calorimetry and urinary nitrogen excretion. Plasma insulin and glucose concentrations were measured during the frequent sampling intravenous glucose tolerance test, and SI was calculated by the minimum model method. Systolic blood pressure and heart rate were slightly but not significantly higher in OHyp than ONorm but the groups did not differ in fasting plasma insulin or glucose concentrations, carbohydrate or lipid oxidation, lean and fat mass, bone mineral content, or distribution of body fat. By contrast, SI was significantly lower in OHyp than ONorm (8.2 [0.7] vs 13.4 [1.5] 10(-4) L mU-1 min-1, p < 0.01). Within the whole study population upper-body fat mass was positively correlated with fasting plasma insulin (r = 0.33, p < 0.03) and lipid oxidation was positively correlated with SI (r = 0.35, p < 0.04) and negatively correlated with subscapular/triceps skinfold thickness (r = -0.43, p < 0.01). Thus, impairment of SI precedes both the development of overt hypertension and gain or redistribution of body fat. Therefore, the concept that SI is low as a result of altered fat distribution has to be reconsidered, at least in young male offspring of hypertensive parents.

Adipose Tissue↗
PubMed1993

Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension.

To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients [mean body mass index (BMI) 30.2 kg.m-2] had been on prior treatment with a thiazide diuretic in low dosage and/or a beta-adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg.m-2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg once daily in 14 patients who were hypertensive after 8 weeks on the lower dosage. At entry (before placebo), SI was slightly but not significantly lower in group A than B [2.7 vs. 3.6 x 10(-4) ml.microU-4.min-1]; fasting plasma insulin was 13.6 vs. 12.9 microU.ml-1. After 6 weeks on placebo, S1 averaged 3.7 in group A and 4.4 x 10(-4) microU.ml-1.min-1 in group B; fasting plasma insulin was 14.6 vs. 15.1 microU.ml-1, and glucose 5.5 vs. 5.5 mmol.l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine↗
PubMed1993

Pathogenesis and treatment of hypertension associated with diabetes mellitus.

The pathogenesis of hypertension associated with diabetes mellitus (DM) involves an interplay of hereditary and acquired mechanisms. A familial trait for essential hypertension appears to be a risk factor for the development of both hypertension and nephropathy in type I DM and coexists commonly with impaired insulin sensitivity, relative hyperinsulinemia, and dyslipidemia, which can already be detected before the appearance of hypertension, obesity, or upper abdominal redistribution of body fat. The latter finding helps explain the frequent development of hypertension as well as dyslipidemia and/or type II DM in given individuals. Obesity is an important factor promoting these complications. Type I or II DM but not uncomplicated essential hypertension is characteristically accompanied by excess body Na+. This abnormality complements a tendency toward vascular hyperreactivity and a presumably morphologic and functional vasculopathy, thereby promoting the pathogenesis of hypertension in diabetic patients. For the treatment of hypertension in diabetic patients, nonpharmacologic measures are indispensable. If drugs are needed, angiotensin-converting enzyme (ACE) inhibitors and some but not all calcium antagonists are the preferred agents. Monotherapy or a combination of these drug types allows effective blood pressure control in most diabetic patients without further metabolic impairment; ACE inhibitors even tend to improve glucose control. Ketanserin may be a potential alternative, and if a diuretic is also needed, the metabolically neutral indapamide is a reasonable choice. If these agents do not allow satisfactory blood pressure highly selective beta 1-blockers or alpha 1-blockers may be introduced as a second choice. In diabetic patients with nephropathy, effective antihypertensive therapy can reduce proteinuria and slow the progression of the nephropathy; ACE inhibitors may improve diabetic proteinuria even at unchanged systemic blood pressure levels. Unless diuretics are needed for reasons other than hypertension, the treatment of diabetic patients with thiazides or loop diuretics in conventional dosage should probably be avoided until clarification of their influence on prognosis. Nevertheless, whether and to what extent other agents and nonpharmacologic measures can modify the prognosis in diabetic patients is also unclear, and the approach to antihypertensive therapy is therefore still largely empiric.

Antihypertensive Agents↗
PubMed1993

The pathogenesis of hypertension in obese subjects.

Obese subjects are at an increased risk of becoming hypertensive and vice versa. Essential hypertension and obesity are commonly accompanied by insulin resistance (defined as impaired insulin-mediated glucose disposal) and hyperinsulinaemia. In the offspring of patients with essential hypertension, insulin resistance and hyperinsulinaemia, as well as related increases in serum low density lipoproteins and triglycerides, often occur prior to the development of essential hypertension, overweight or central redistribution of body fat. Moreover, once obesity, and in particular central obesity, is present, insulin resistance is more marked in hypertensive than in normotensive obese subjects. Hyperinsulinaemia and/or insulin resistance in turn promote body fat deposition and impaired glucose tolerance. This cycle helps to explain why a familial predisposition to essential hypertension poses an increased risk of developing not only hypertension but also dyslipidaemia, obesity and non-insulin-dependent (type 2) diabetes. It is still unclear whether insulin resistance and/or hyperinsulinaemia also promote hypertension per se. Regardless of insulin's exact pathogenic role, obesity and/or a high dietary intake of carbohydrates, salt, etc. can induce several potential pressor mechanisms: 1) higher plasma noradrenaline (norepinephrine) and adrenaline (epinephrine) levels, suggesting a higher sympathetic tone in obese than in nonobese subjects, and in hypertensive obese than in normotensive obese subjects; 2) similarly, a tendency to hyperaldosteronism, with largely normal plasma renin activity, in obese hypertensive patients; 3) enhanced sensitivity of blood pressure to salt; 4) increased total blood volume (although it is normal relative to body surface area), leading to increased cardiac output and eventually eccentric left ventricular hypertrophy; and 5) increased cytosolic free Ca++ levels and reduced intracellular Mg++ levels in the blood cells of obese hypertensive patients and patients with non-insulin-dependent diabetes, although this finding cannot necessarily be extrapolated to cationic levels in vascular muscle cells. Total peripheral vascular resistance is usually low in normotensive obese subjects and rises with the development of hypertension; compared with lean patients with essential hypertension, obese hypertensive patients tend to have a slightly lower level of total peripheral vasoconstriction and a slightly higher cardiac output. Considering the intimate association between essential hypertension and obesity, as well as the prevalence and prognostic relevance of this combination, the spectrum of accompanying metabolic and cardiovascular abnormalities deserves careful consideration in the evaluation of therapeutic care for such patients.

Humans↗
PubMed1993

Serum lipoproteins during treatment with antihypertensive drugs.

Several drugs used for antihypertensive therapy may modify the lipoprotein metabolism. Thiazides in high dosage and loop diuretics can increase serum low-density lipoprotein (LDL) cholesterol and/or very-LDL cholesterol and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio, while HDL cholesterol is largely unchanged; triglycerides (Tg) are also often elevated. Premenopausal women may be protected from this side effect. Whether diuretic-induced dyslipidemia is dose-dependent and low thiazide doses (i.e., hydrochlorothiazide < or = 12.5 mg daily) are interacting less, awaits clarification. beta-Blockers without intrinsic sympathomimetic activity increase serum triglycerides and tend to lower the potentially antiatherogenic HDL cholesterol. The diuretic-antihypertensive agent indapamide, given at a dose of 2.5 mg/day, is neutral with regard to serum lipoprotein and glucose metabolism. The potassium-sparing diuretic spironolactone, conventional sympatholytic agents, calcium-channel blockers, and probably the serotonin2-receptor antagonist ketanserin, exert no relevant effects on the lipoprotein profile. Angiotensin-converting enzyme inhibitors may slightly decrease serum triglycerides. alpha 1-Receptor blockers slightly decrease LDL cholesterol and Tg and increase HDL cholesterol. Drug-induced development or aggravation of dyslipidemia represents a potentially adverse influence. In the hypertensive population, effective blood pressure control with traditional drug therapy based on thiazide-type diuretics in high dosage led to a distinct decrease in cerebrovascular morbidity and mortality, but failed to satisfactorily reduce coronary complications. The prognostic relevance of drug-induced changes in serum lipoproteins, carbohydrate metabolism and other risk factors or correlates awaits further clarification.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗