N K Hollenberg

..The answer, of course, is that it can be either, neither, or both, at least before treatment is undertaken. Once treatment is undertaken, all patients have an element of kidney involvement...

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..Although it is widely recognized that there are familial elements in the pathogenesis of hypertension, remarkably little is known about the influence of family history on response to specific antihypertensive agents...

..If research already under way supports these early suggestions, then eprosartan will be an important addition to our therapeutic armamentarium...

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..Future studies should focus on other commonly consumed subclasses (eg, anthocyanins and flavanones), examine dose-response effects, and be of long enough duration to allow assessment of clinically relevant endpoints...

..This constellation is generally attributed to predominant efferent arteriolar dilation...

..We aimed to investigate whether high doses of valsartan, an angiotensin receptor blocker, are superior to conventional doses to reduce urinary albumin excretion rates (UAER) in such patients...

..One study pointed to a role for renin-system activation. In the other study, the pattern of renal hemodynamics was compatible with a renin mechanism...

..Further investigation of NO-targeted therapies in these diverse diseases is clearly mandated...

..Evidence for renin-system activation in many patients with type 1 diabetes mellitus has raised the possibility that aldosterone-widely recognized as a contributor to vascular injury-could play a role...

..The next decade will be interesting...

..On the bright side, prognosis is improved substantially by the array of antihypertensive drugs available today...

..Genes governing renin substrate (angiotensinogen) production showed gene polymorphisms in nonmodulators. As nonmodulation occurs in approximately 40% of patients with essential hypertension, clearly other genes must contribute...

..The renin system is important in patients with diabetes mellitus because so many relevant factors converge on the intrarenal renin system...

..Life satisfaction is less influenced, possibly providing a measure of the degree of stress...

..ARBs are currently undergoing clinical trials to assess their efficacy in hypertensive patients with nephropathy...

..Endothelial dysfunction with loss of nitric oxide production is a common feature in many cardiovascular diseases. This fascinating class of drugs continues to provide us with new and important therapeutic opportunities...

..PRA did not change with hyperglycemia. Enhancement of renal vasodilation during hyperglycemia by captopril without alteration of PRA suggests activation of the intrarenal renin angiotensin system...

..The enhancement of the renal vasodilator effect of eprosartan during hyperglycemia is consistent with activation of the intrarenal renin-angiotensin system...

..As obesity is a common finding in diabetic individuals, and obesity has been linked to an increase in plasma angiotensinogen levels, we enrolled diabetic subjects with a wide range of body mass index (BMI) for this study...

..Despite their increased risk of nephropathy, remarkably little is known about renal perfusion and function in healthy African Americans...

..Mechanisms protecting against a blunted adrenal response to Ang II in young white women are absent in blacks. These differences may contribute to the markedly increased prevalence of hypertension in young black women...

..The high correlation between the renal hemodynamic response to captopril and to candesartan indicates that reduced angiotensin II formation is the main mechanism of action of the ACE inhibitor...

..The factors that mediate enhanced adrenal response to Ang II with sodium restriction may be defective, suggesting the existence of alternative physiological mechanisms for sodium homeostasis in the low-renin state...

..In this study we tested the hypothesis that variation in the renal vasodilator response to ACE inhibition in healthy humans reflected the variation in angiotensin-mediated renal vasoconstriction provoked by a low-salt diet...

..We conclude that the nonmodulating trait may be a heritable defect that leads to the development of hypertension and is not an epiphenomenon...

..This "override" of genotype, manifest by a very low frequency of non-modulation in young women, may participate in their known protection against cardiovascular disease...

..Under the conditions of this study, ACE inhibition led to nonuniform changes in the response to exogenous Ang I, suggesting intrarenal conversion of Ang I to Ang II...

..This increase could account for suppressed circulating renin, the exaggerated renal vasodilator response to irbesartan, and the therapeutic effectiveness of interrupting the renin system in diabetic nephropathy...

..The infrequency of a low renin state, and the inappropriately high renin levels on a high salt intake, provide a rational basis for pharmacologic interruption of the renin system to treat patients with type II diabetes...

..This study was designed to see if insulin resistance in hypertensives, measured using the HOMA index, differs, based on salt sensitivity, renin status and sodium intake...

..In conclusion, the present study suggests that digitalis-like factor may provide a link between hypertension and cataract formation...

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..Thus, eprosartan probably exerted its effect via the angiotensin receptor. More complete blockade of the renin system can be achieved by pharmacological interruption at this level, a finding that could have therapeutic implications...

..The results are consistent with a role for a circulating digitalis-like factor in this volume-dependent model, but events at the VSM level are complex...

..The findings indicate that the VSM contractile response induced by the agent isolated from PD reflects VSM sodium pump inhibition, supporting its candidacy as a circulating regulator of the sodium pump...

..Accumulating evidence suggests that the abnormality is inherited and may be the most common form of hypertension...

..From a renoprotective perspective, the ARB appear to have tremendous potential in the management of hypertension...

..We believe that the potential of renin inhibition in human therapy has been under estimated and still shows substantial promise...

..Together, these experiments demonstrate that the PD candidate specifically, and reversibly, inhibits the sodium pump via the cardioglycoside binding site, and hence, meets this crucial criterion for candidacy...

..Because angiotensin receptor blockers do provide this specific blockade, they offer far more promise than ACE inhibitors...

..These findings are compatible with a role for one or more endogenous sodium pump inhibitors as the determinant of vascular smooth muscle tone in the volume-sensitive hypertension of renal disease...

..Increased renal sodium pump activity in DOCA high salt animals would, if unmitigated, favor sodium reabsorption and may contribute to hypertension...

..This suggests that the expression of the nonmodulating phenotype, presumably secondary to changes in the expression of the angiotensinogen gene, is modulated by female sex hormones...

..NM had elevated fasting insulin levels compared to M, compatible with an insulin resistant state, but this insulin resistance are dissociable in the hypertensive population...

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..Thus, the sodium retaining tendency of nonmodulators may reflect, at least in part, a reduction in intrarenal dopamine production in response to a sodium load...

..Effective and early blockade of this system is therefore an important aspect of management...

..We conclude that the factors that influence sensitivity of BP to salt intake do not influence the systemic or renal hemodynamic response to ACE inhibition...

..Reductions in aldosterone or hypertension might reduce alpha2 in the heart. Only the renal response would favor sodium reabsorption, which could contribute to the hypertensive process...

..To test utility of cystatin-C as a marker of glomerular filtration rate during pregnancy, we performed serial correlations with inulin clearance during pregnancy and postpartum...

..Moreover, the application of stringent criteria to the confusing array of factors in plasma that may affect assays for DLF appears to reduce the field dramatically, to a single candidate in this setting...

..DLF in at least three different patient populations probably represents identical chemical species.(ABSTRACT TRUNCATED AT 250 WORDS)..

..Comparison of adverse reactions provides an incomplete measure of how well a drug is tolerated. In contrast, findings indicate that even subtle CNS-mediated effects on mood and well-being can be detected by quality-of-life evaluation...

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..The observations strengthen the hypothesis that supersensitivity of collateral arterial vessels to serotonin reflects a 5-HT2 receptor mechanism...

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..Thus, Thy-1 appears to be a marker of adult but not embryonic angiogenesis. The upregulation of Thy-1 by cytokines but not growth factors indicates the importance of inflammation in the pathogenesis of adult angiogenesis...

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..We predicted that blockade with the direct oral renin inhibitor aliskiren would produce renal vascular responses exceeding those induced by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers...

..1+/-17.6 ml/minute/1.73 m2). When it was above the median, the RPF response was also larger (62.2+/-13.9 ml/minute/1.73 m2; p=0.006). Renin response to ACE-I and ARB confirms activation of the RAS in diabetic patients...

..The relevant and necessary studies are ongoing...

..Further studies are warranted to address this balance in states of insulin resistance and the possible implications for the association of insulin resistance with risk for chronic kidney disease...

..With the modalities of transcranial Doppler and MRI, we have the capabilities of analyzing the potential benefits of flavanols on brain perfusion and, subsequently, on cognition...

..However, there are many risk factors and an observational study cannot provide definitive evidence...

..For many patients, this is likely to lead to improved treatment...

..In many patients, this is likely to lead to improved treatment...

..We aimed to determine if the TZD rosiglitazone could reduce RAS activation...

..Animal models suggest that the renal vasculature of men may be significantly more dependent on nitric oxide than that of women...

..We have previously shown that flavanol-rich cocoa induced peripheral vasodilation, improving endothelial function via a nitric oxide (NO)-dependent mechanism...

..72; p=0.008). Conversely, HbA1C correlated with none of the measures of renin system activation (r=0.05;p=0.7). In type 1 diabetic subjects, short-term hyperglycaemia, but not long-term glycaemic control, enhanced the RR to captopril...

..Among dietary factors that varied among migrating Kuna, the notably higher intake of flavanol-rich cocoa is a potential candidate for further study...

..Collectively, our data demonstrate that the human ingestion of the flavanol (-)-epicatechin is, at least in part, causally linked to the reported vascular effects observed after the consumption of flavanol-rich cocoa...

..For this subclass of essential hypertension, it is likely that genotyping can be substituted for complex phenotyping for therapeutic and preventive decision making...

..The validity of this approach relative to the homogeneity of sodium-sensitive hypertension was investigated while simultaneously controlling multiple putative factors...

..The effectiveness of ramipril in reducing minimum FVR and urinary albumin excretion in NMHT also suggests a common mechanism...

..The mechanism involved may contribute to the increased susceptibility to renal injury in blacks...

..The complex interrelationships between hyperglycemia, insulin, NO, and the RAS may result in phenotypes that indicate varying risk of diabetic nephropathy and underlying genetic polymorphisms...

..We examine herein angiotensinogen (AGT) as a candidate gene to help elucidate potential mechanisms for previously reported AGT linkage and association studies...

..Cocoa can contain extraordinary concentrations of flavanols, a flavonoid subclass shown to activate nitric oxide synthase in vitro...

..Diagnoses of NYHA class III and IV CHF were not studied in clinical trials of TZDs, and thus TZDs are not recommended for patients with CHF of this severity...

..Increased susceptibility to glomerular hyperfiltration of African Americans on a high salt intake may explain their proclivity to progressive renal injury associated with essential hypertension...

..Weight loss should be considered in the overweight or obese patient for renal protection...

..RAS activation occurs in healthy women using oral contraceptives (OCs), but the effects of OC use on the diabetic kidney are unclear...

..CONCLUSIONS: Evidence is mounting to support cardiovascular health benefits from the consumption of flavanol-rich cocoa. This review hopes to illuminate sound scientific principles by which future research in the field can be guided...

..Our aim was to determine the degree to which the non-ACE pathways contribute to RAS activation in type 1 diabetes mellitus (DM)...