Obesity and kidney disease: Beyond the hyperfiltration.

In industrialized countries, overweight and obesity account for approximately 13.8% and 24.9% of the kidney disease observed in men and women, respectively. Moreover, obesity-associated glomerulopathy is now considered as "an emerging epidemic." Kidney function can be negatively impacted by obesity through several mechanisms, either direct or indirect. While it is well established that obesity represents the leading risk factor for type 2 diabetes and hypertension, awareness that obesity is associated with direct kidney damage independently of hypertension and diabetes is still not widespread. In this paper we will discuss the emerging role of adipose tissue, particularly in the visceral depot, in obesity-induced chronic kidney damage.

The possible role of glutathione-S-transferase activity in diabetic nephropathy.

The most common cause of end stage renal disease is diabetic nephropathy. An early diagnosis may allow an intervention to slow down disease progression. Recently, it has been hypothesized that glutathione-S-transferase (GST) activity may be a marker of severity of chronic kidney disease. In particular, a lower GST activity is present in healthy subjects compared to patients with nephropathy. In the present review we illustrate the scientific evidence underlying the possible role of GST activity in the development of diabetic nephropathy and we analyze its usefulness as a possible early biomarker of this diabetic complication.

Gut hormones and endothelial dysfunction in patients with obesity and diabetes.

Overweight and obesity are the fifth leading risk for global deaths and its prevalence has doubled since 1980. At least 2.8 million adults, worldwide, die each year as a result of being overweight or obese. The deleterious effects of obesity are tightly related to diabetes, as they are often clinically present in combination to confer increased cardiovascular mortality. Thus, patients with diabetes and obesity are known to develop accelerated atherosclerosis characterized by a dysfunctional endothelium and decreased nitric oxide bioavailability. Recent clinical studies support, indeed, the use of incretin-based antidiabetic therapies for vascular protection. Thus, attention has been focusing on gut hormones and their role, not only in the regulation of appetite but also in vascular health. Intervention directed at modulating these molecules has the potential to decrease mortality of patients with diabetes and obesity. This review will cover part of the ongoing research to understand the role of gut hormones on endothelial function and vascular health.

Obesity, inflammation and endothelial dysfunction.

Cardiovascular disease is the leading cause of morbidity and mortality in obese individuals. Obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to originate from disruption in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, impair vascular homeostasis and lead to endothelial dysfunction. An altered endothelial cell phenotype and endothelial dysfunction are common among all obesity-related complications. A crucial aspect of endothelial dysfunction is reduced nitric oxide (NO) bioavailability. A systemic pro-inflammatory state in combination with hyperglycemia, insulin resistance, oxidative stress and activation of the renin angiotensin system are systemic disturbances in obese individuals that contribute independently and synergistically to decreasing NO bioavailability. On the other hand, pro-inflammatory cytokines are locally produced by perivascular fat and act through a paracrine mechanism to independently contribute to endothelial dysfunction and smooth muscle cell dysfunction and to the pathogenesis of vascular disease in obese individuals. The promising discovery that obesity-induced vascular dysfunction is, at least in part, reversible, with weight loss strategies and drugs that promote vascular health, has not been sufficiently proved to prevent the cardiovascular complication of obesity on a large scale. In this review we discuss the pathophysiological mechanisms underlying inflammation and vascular damage in obese patients.

Enhanced endothelium-dependent vasodilation in Fabry disease.

BACKGROUND AND PURPOSE: Fabry disease is an X-linked lysosomal storage disease secondary to deficiency of alpha-galactosidase A with resulting glycolipid accumulation, particularly globotriaosylceramide in arterial smooth muscle and endothelial cells. A systemic vasculopathy, including early-onset stroke, is prevalent without a clear pathogenesis. METHODS: Seventeen normotensive and normocholesterolemic hemizygous Fabry patients (aged 21 to 49 years) and 13 control subjects (aged 21 to 48 years) were investigated by venous plethysmography, allowing assessment of forearm blood flow. Plethysmographic measurements were obtained at baseline and during intra-arterial infusion of acetylcholine and sodium nitroprusside both with and without N(G)-monomethyl-L-arginine (L-NMMA). RESULTS: Forearm blood flow was significantly higher in patients than in control subjects at all 3 acetylcholine doses (P=0.014). Patients had a greater response to acetylcholine even after the addition of L-NMMA (P=0.036). CONCLUSIONS: These results demonstrate an increased endothelium-mediated vascular reactivity in Fabry disease. The increased vessel response to acetylcholine with and without L-NMMA suggests altered functionality of non-NO endothelium-dependent vasodilatory pathways.

No cardiovascular effects of single-dose pseudoephedrine in patients with essential hypertension treated with beta-blockers.

OBJECTIVE: The use of the decongestant pseudoephedrine has been cautioned in patients with arterial hypertension, due to the possible rise in blood pressure induced by the sympathostimulatory properties of the drug. This effect could be enhanced in hypertensives treated with beta-blockers, in whom the vasoconstrictor effect of alpha-adrenergic stimulation is unbalanced. The purpose of this study was to investigate the cardiovascular response to pseudoephedrine in hypertensive patients treated with different types of beta-blockers. METHODS: We recruited 29 (18 males) mild-to-moderate essential hypertensive patients [mean age 49(2) years] in a randomized, placebo-controlled, crossover trial. All participants received either placebo, or a nonselective (propranolol 160 mg once daily) or a selective (atenolol 100 mg once daily) beta-blocker for 1 week. At the end of each period, all patients received a single oral dose of pseudoephedrine (60 mg) and their blood pressure and heart rate were monitored at repeated intervals for 2 h. RESULTS: After 1 week of propranolol or atenolol, patients had significantly lower systolic blood pressure and heart rate than after placebo, whereas diastolic blood pressure was not significantly modified. The acute administration of pseudoephedrine did not change systolic and diastolic blood pressure and heart rate from baseline at the end of any of the treatment periods. CONCLUSIONS: A standard oral dose of pseudoephedrine does not significantly affect blood pressure values in hypertensive patients treated with beta-blockers, and therefore may be safely used in this subset of patients.

Relation of stress testing and ambulatory blood pressure to hypertensive cardiac damage.

In essential hypertension, the severity of cardiovascular damage is only weakly related to clinic blood pressure (BP), whereas a better relationship seems to exist with BP recorded during stressful situations. The present study compared BP levels measured during laboratory stress testing and 24-h ambulatory monitoring with regard to their relationship with cardiac end-organ involvement. BP recorded during a mental and a physical challenge and during 24-h ambulatory monitoring was related to Doppler echocardiography characteristics of left ventricular structure and filling in 63 untreated essential hypertensives and in 32 healthy subjects. In the hypertensive group, only a weak relationship was observed between left ventricular mass and clinic BP; the strength of this association was not improved by BP measured during mental task and cycle ergometry, and was slightly but not significantly higher for BP recorded during ambulatory monitoring. In multivariate analysis, left ventricular mass was independently predicted by stroke index and 24-h systolic BP. Among the different pressure measures, 24-h, daytime, and nighttime BPs bore the only significant relation to relative wall thickness. In the normotensive group, no significant relationship was observed between left ventricular mass and different measures of BP. Doppler indexes of left ventricular diastolic filling did not significantly relate to any BP measurement in the hypertensive group, and generally bore a significant inverse relationship to various BP recordings in the normotensive group. To summarize, stress testing BP does not help in identifying hypertensive patients with increased left ventricular mass.

Postprandial Hemodynamic Changes in Hypertensives Treated with Calcium Antagonists or ACE Inhibitors.

Our aim was to investigate possible abnormalities in postprandial hemodynamic changes in hypertensives treated with different vasodilating drugs, calcium antagonists, or angiotensin-converting enzyme inhibitors. Eleven healthy subjects and 22 hypertensive patients effectively treated with an angio tensin-converting enzyme inhibitor (ACEI) (n = 9) or calcium antagonists (n = 13) were studied. Cardiac output and blood pressure were monitored every 20 min from 2 h before lunch to 3 h after using a computer-assisted impedance cardiograph coupled with an automatic blood pressure monitor. After meals, a significant decrease in mean arterial pressure (minus sign7.9% plus minus 2.1) was observed in ACEI-treated hypertensives when compared with the minor changes observed in calcium-antagonist-treated hypertensives (minus sign3.7% plus minus 1.5) and in normotensives (minus sign2.7% plus minus 1.5). When compared with normotensives, the patients treated with ACEI showed a larger postprandial fall in total peripheral resistance index (minus sign20.8% plus minus 3.4 versus minus sign15.3% plus minus 4.1) with a larger increase in heart rate (11.3% plus minus 2.3 versus 8.1% plus minus 1.3). In hypertensives treated with calcium antagonists, the postprandial hemodynamic changes appeared blunted and not significant. Different antihypertensive drugs appear to have different effects on the postprandial hemodynamic changes.

Psychophysiological reactivity and cardiac end-organ changes in white coat hypertension.

This study aimed 1) to assess whether patients with an exaggerated blood pressure response to the doctor's presence ("white coat" effect) also display a pattern of enhanced blood pressure reactivity to mental stress and physical exercise and 2) to determine the presence of left ventricular structural and filling abnormalities in patients with white coat hypertension. We studied 56 (40 men) consecutive patients (mean [SD] age, 46.4 [9.1] years) whose clinic blood pressure was repeatedly high. Patients were classified as having white coat hypertension (n = 20) if both their mean daytime (from 7 AM to 11 PM) ambulatory systolic and diastolic blood pressures were less than 134 and 90 mm Hg, respectively. Patients were considered to have persistent hypertension (n = 36) if daytime systolic blood pressure was 134 mm Hg or more or diastolic blood pressure was 90 mm Hg or more. Eighteen subjects with clinic blood pressure lower than 140/90 mm Hg served as a normotensive control group. Blood pressure reactivity from baseline to mental arithmetic, isometric handgrip, and cycle ergometry did not display any difference among the three groups. The white coat hypertensive group had left ventricular mass index lower than the persistent hypertensive group but higher than the normotensive group. Doppler indexes of left ventricular diastolic filling displayed similar abnormalities in the white coat and persistent hypertensive groups compared with the normotensive group.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the effects of terazosin and enalapril on laboratory stress testing blood pressure in patients with essential hypertension.

It is the current opinion that an ideal antihypertensive drug should reduce blood pressure (BP) not only at rest but also during stressful situations. The current study was aimed to compare the effects of the selective alpha 1-adrenergic blocker terazosin (5 mg once daily) and of the angiotensin-converting enzyme inhibitor enalapril (20 mg once daily) on cardiovascular response to a set of standardized laboratory stressors, such as mental arithmetic, handgrip test and cycle ergometry, in a group of 16 essential hypertensive patients. The study was a randomized, double-blind, cross-over trial preceded by a placebo run-in period. Terazosin and enalapril had a comparable effect on resting BP, reducing systolic (SBP) and diastolic (DBP) blood pressure from 159.5 +/- 13.9/101.6 +/- 8.8 mm Hg during placebo by 7.8%/6.7% and by 11.3%/10.2%, respectively. The "response" rate to the two treatments was approximately the same, being 69% and 75% after terazosin and enalapril, respectively. During mental arithmetic, from an average of 181.6 +/- 17.8/118.6 +/- 11.5 mm Hg during placebo, BP was reduced by 11.5%/7.9% after terazosin and by 13.6%/8.5% after enalapril; during handgrip test, BP decreased from 207.2 +/- 22.2/142.2 +/- 13.6 mm Hg by 7.3%/8.4% after terazosin and by 7.7%/7.1% after enalapril; finally, during cycle ergometry, terazosin and enalapril lowered BP by 5.4%/6.7% and 7%/3.1%, respectively, from a placebo value of 215.5 +/- 17.3/127.6 +/- 11.2. No significant difference in antihypertensive efficacy was observed between the two drugs, either at rest and during stress testing.(ABSTRACT TRUNCATED AT 250 WORDS)