Impairment of Renal Vasodilation With l -Arginine Is Related to More Severe Disease in Untreated Hypertensive Patients

Abstract

Abstract-Data remain insufficient to place the decreased response to L-arginine in hypertensive patients within a consistent pathophysiological sequence. The aim of the present study in patients with essential hypertension was to assess the relationships between the response to L-arginine and a set of relevant clinical and laboratory parameters. In this prospective, interventional study, we administered L-arginine to untreated hypertensive individuals and healthy control subjects and measured the clearance of inulin and of para-aminohippurate and a set of biochemical and clinical variables. L-Arginine infusion revealed major differences between control subjects and 1 subgroup (group B) of hypertensive individuals. Group B hypertensives (nϭ18) had no increase in inulin clearance and no decrease in renal vascular resistance with L-arginine; however, in another subset of hypertensive patients (group A, nϭ27), the insulin clearance increased and renal vascular resistance decreased similar to the control group (group C, nϭ11). The ambulatory blood pressure monitoring in group B showed both an increased mean diastolic pressure and a "nondipper" pattern in the nocturnal regulation of arterial pressure. These findings in group B were accompanied by significant alterations in optic fundus and left ventricle hypertrophy and increased microalbuminuria (all, PϽ0.05). Furthermore, group B individuals had significantly lower values of HDL cholesterol and a higher baseline atherogenic index, plasma insulin level, and glucose/insulin index. We disclose a previously undescribed relationship between end organ repercussion and decreased renal hemodynamic response to L-arginine. Our results may help to understand the mechanisms that lead to target organ damage in hypertension. Key Words: L-arginine Ⅲ hypertension, essential Ⅲ endothelium Ⅲ blood pressure monitoring, ambulatory D espite intense investigative efforts, major basic aspects of the pathophysiology of essential hypertension remain unclear. In recent years, a great deal of attention has been paid to the involvement of endothelium-related mechanisms in the pathogenesis of arterial hypertension. [1][2][3][4][5][6][7][8] In particular, the role of the vascular and renal regulatory mediator NO in hypertension has been extensively studied through the administration of the NO precursor amino acid L-arginine. 9 -12 In these studies, an alteration in the renal vasodilatory response to L-arginine was described, although the findings that have been reported are less than homogeneous. 9 -12 Therefore, even though the information provided in the aforementioned studies is relevant, the data obtained are incomplete and still must be organized to provide a coherent pathophysiological interpretation. First, to homogenize the information and to eliminate undesired variability, strict criteria are necessary to select patients with essential hypertension. Second, and of extreme importance, no relationships have been sought between the response to L-arginine and markers of severity of hypert...

Magnetic Resonance Measurements of Renal Blood Flow and Disease Progression in Autosomal Dominant Polycystic Kidney Disease

“…The results of the study suggest that the presence of hypertension or factors related to hypertension and reduced levels of HDL cholesterol likely play a role. In essential hypertension, a decreased renal vasodilatory response to l-arginine has been associated with decreased serum levels of HDL cholesterol (37). The study unexpectedly detected a positive, rather than a negative, effect of serum uric acid, a factor that has been proposed to play a role in the development of renal microvascular disease (38), on the RBF slopes.…”

Hyperhomocysteinemia Induces Renal Hemodynamic Dysfunction

“…With the exception of microalbuminuria, neither clinical nor laboratory variables can be reliably used to differentiate patients with progressive renal injury from those who follow a more benign evolution (47). Using low doses of L-Arg and L-NAME, several investigators have been able to avoid changes of arterial BP, and thus could dissociate the direct (renal) effects of NO from the indirect effects (46) resulting from changes in systemic BP.…”

“…L-Arg has been shown to induce renal vasodilation by promoting NO formation in the kidney. Despite the sparsity of evidence about the real importance of the altered renal vasodilatory response to L-Arg, it could be proposed that the L-Arg study is sensitive enough to detect subtle endothelium-related renal hemodynamic changes (47). Thus, the attenuated response to L-Arg observed in HYC rats suggests that a higher superoxide anion radical production induced by hyperhomocysteinemia favors a greater NO inactivation by sequestration, which, in turn, reduces the ability of NO to produce renal vasodilation.…”

l-Arginine-Induced Vasodilation of the Renal Vasculature Is Preserved in Uremic Type 1 Diabetic Patients After Kidney and Pancreas but not After Kidney-Alone Transplantation

“…To the best of our knowledge, this is the first study that addresses the use of MR flow analysis in assessing the renal vasodilatory reserve in transplanted renal arteries after L-arginine infusion. Bello et al (14) found a greater renal vasodilatory response to L-arginine infusion in normal subjects and in hypertensive patients without complications than in hypertensive patients with more severe disease. In a previous study (29), the increase in renal flow was similar to the variation we found in our work in the control group and in KP patients, although we used a different method to calculate renal flow.…”

“…Infusion of L-arginine and subsequent measurements of changes in renal hemodynamics have been used for studying the endothelial-dependent dilation of the renal vasculature. The infusion of Larginine, inducing an endothelial response, determines vasodilation only when the vasomotory properties of the vessels are preserved (14). The endothelium-dependent vasodilation during infusion of L-arginine has been reported in renal arteries (14), brachial arteries (15), coronary arteries (16), and bypass grafting (17) using various techniques, such as para-amino-hippurate clearance (14), Doppler ultrasound (15), or angiography (16).…”