Search

Reversal by the mineralocorticoid receptor antagonist spironolactone on cardiac eand renal abnormalities, associated with long-term (since weaning) administration of a high (2 and 8% NaCl chow, HS2 and HS8) sodium diet, was assessed in Sprague-Dawley rats. At the age of 5 mo, spironolactone (20 or 100 mg/kg, gavage) or placebo were given for 14 days to HS2 and HS8 rats. A group fed a regular diet (0.8% NaCl, NS) remained untreated. High sodium intake had no detectable effect on blood pressure; however, cardiac mass index and cross-sectional area of the carotid artery, as well as albuminuria, were increased only in the HS8 group compared with the control group on NS diet. In addition, a marked reduction in glomerular filtration rate (by 40%), associated with a nonproportional fall in renal plasma flow (thus resulting in a decrease in filtration fraction), was observed only in the HS8 group. No change in cardiac and renal fibrosis was detected. Production of the reactive oxygen species (ROS) by aortic tissue was increased in HS8 rats, whereas ROS production by the heart was unaffected. Only the high dose of spironolactone was effective, as it markedly reversed the cardiac hypertrophy and renal hypofiltration associated with the HS8 feeding. The changes were observed in the absence of any effect on systemic blood pressure and production of ROS. These observations favor aldosterone's role in the deleterious effects of marked and prolonged increases in sodium intake. spironolactone; renal function; reactive oxygen species; cardiac hypertrophy

The influence of a low-sodium (LS) diet was assessed on the cardiac and renal alterations and pro-oxidant effect associated with a 10-day infusion of angiotensin II (200 or 400 ng*[kg.sup.-1]*[min.sup.-1], osmotic pumps). Tail-cuff pressure (TCP), albuminuria, and renal blood flow were determined at the end of the experiments. Heart weight index (HWI) and production of superoxide anion ([O.sup.-.sub.2].) by the left ventricle and [H.sub.2][O.sub.2] by the aorta was measured with the use of bioluminescence. Although the final TCP was similar in LS and normal sodium (NS) rats infused with high and low doses of angiotensin II, respectively, the increase in HWI was prevented by the LS diet. Sodium restriction reduced the rise in albuminuria without a change in the renal effect of angiotensin II. The increased production of [O.sup.-.sub.2] and [H.sub.2][O.sub.2] observed in NS rats was abrogated in LS rats. The beneficial influence of dietary sodium restriction on target organ damage induced by angiotensin II is independent of arterial pressure reduction and possibly related to attenuation of the prooxidant effect of the peptide. heart weight; albuminuria; reactive oxygen species; renal hemodynamic

Studies to quantitatively assess the degree of afferent arteriolar (AA) connectivity using an HCl maceration-microdissection method in rat, rabbit, mouse and human renal vasculatures reveals the arrangement of 51 to 60% of the total AA populations into vascular units, with the origin and joining arterial unit being shared by two AAs in all the species studies. The non-random pattern of recin distribution and correlation between arteriolar lengths within anatomic pairs indicates an association between the endocrine functions of paired arterioles.

An evaluation of the combined effects of losartan and enalapril on the renal adjustment to dietary sodium elimination in normal rats reveals that losartan-induced renal sodium elimination is affected by enalapril due to angiotensin-regulated processes. Non-angiotensin associated effects of enalapril facilitate a renal function reduction in sodium-restricted animals. High doses of losartan are required to damage the renal adjusting process, indicating that the tubular renin-angiotensin system is vital for renal adjustment to dietary sodium elimination.

Changes in the systemic and renal adaptation to dietary sodium restriction of the renin-angiosten system due to age were investigated. Mean arterial pressure and plasma renin activity were monitored in 10-, 20- and 30-month old female rats prior to and during sodium restricted diets. The relationship of dietary sodium restriction to arterial pressure and sodium conservation was established.

The effect of endogenous angiotensin II on the increase in hematocrit induced by atrial natriuretic peptide (ANP) was examined on nephrectomized rats. Endogenous angiotensin II modulated the effect of ANP on vascular permeability. This was attributed to the supression of angiotensin II generation and antagonism of its receptors which abolishes the effect of ANP on hematocrit. The result suggests a possible role for tissue renin-angiotensin interaction in controlling endogenous ANP on transcapillary shift and formation of edema.

Classical studies indicate that the contribution of kidneys to hypertension is almost exclusively related to the association between mean arterial pressure (MAP) and vascular resistance. Recent reports including estimates of glomerular filtration rate (GFR) have shown that pulse pressure (PP) and pulse wave velocity, 2 major indices of arterial stiffness, now emerge as significant predictors of cardiovascular risk and age-associated decline in GFR. Such findings are mainly observed in patients with hypertension and renal failure and in atherosclerotic subjects undergoing coronary angiography. In such patients, amplification of PP between ascending and terminal aorta at the renal site is constantly increased over 10mm Hg (P < 0.001), whereas MAP level remains continuously unmodified. This PP amplification is significantly associated with presence of proteinuria. Furthermore, increases in plasma creatinine and aortic stiffness are independently and positively correlated (P < 0.001) both in cross-sectional and longitudinal studies. All these relationships associating PP, arterial stiffness, and renal function are mainly observed in patients 60 years of age or older. Furthermore, in renal transplant patients and their donors, subjects have been recruited for evaluations of arterial stiffness and posttransplant decline in GFR. Determinants of GFR decline were evaluated 1 and 9 years after transplantation. The first year GFR decline was related to smoking and acute rejection, whereas the later was significantly and exclusively associated with donor age and aortic stiffness. Thus, in hypertensive humans, the observed association between PP and GFR suggests that the 2 parameters are substantially mediated by arterial stiffness, not exclusively by vascular resistance. [ABSTRACT FROM AUTHOR]

After kidney donation, the remaining kidney tends to hyperfiltrate, thus limiting the initial loss of renal function. The potential determinants of this adaptive glomerular hyperfiltration (GHF) and specifically the influence of arterial function are poorly known. In 45 normotensive healthy kidney donors [51 ± 10 yr (mean ± SD), 39 females], glomerular filtration rate (GFR) was measured as the clearance of continuously infused 99mTc-DTPA and timed urine collections at baseline, i.e., before donation, and 1 yr after donation. GHF was computed as postdonation GFR minus half of baseline GFR. Arterial function was assessed as baseline carotid-femoral pulse wave velocity (PWV) and carotid augmentation index (AIx). After kidney donation, no significant change in blood pressure (BP) was observed, but two subjects developed hypertension. GFR decreased from 107 ± 19 to 73 ± 15 ml.min-1.1.73 m-2, and mean GHF was 20 ± 10 ml.min-1.1.73 m-2. In univariate analysis, GHF was inversely correlated to age (r² = 0.24, P = 0.01), baseline PWV (r² = 0.23, P = 0.001), and Aix (r² = 0.11, P = 0.031). Nevertheless, GHF was not correlated to baseline peripheral or central BP. In multivariate analysis, baseline PWV, but not AIx, remained inversely correlated to GHF, independently of age, baseline mean BP, and GFR (model r² = 0.34, P < 0.001). In healthy subjects selected for renal donation, increased arterial stiffness is associated with decreased postdonation compensatory hyperfiltration. [ABSTRACT FROM AUTHOR]