Apocynin per se does not inhibit vascular NADPH-oxidase-dependent superoxide formation. Its in vitro vasodilator actions are not due to NADPH oxidase inhibition but may be explained at least in part by inhibition of Rho kinase activity. The discrepancy between apocynin-induced vasodilation in vitro and the failure of apocynin to lower arterial pressure in SHR suggests opposing effects on arterial pressure-regulating systems in vivo. Its use as a pharmacological tool to investigate vascular NADPH oxidase should be discontinued.

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which in turn decreases ERSNA via activation of the renorenal reflexes in the overall goal of maintaining low ERSNA. We now examined whether the ERSNA-induced increases in ARNA are modulated by dietary sodium and the role of endothelin (ET). The ARNA response to reflex increases in ERSNA was enhanced in high (HNa)- vs. low-sodium (LNa) diet rats, 7,560 +/- 1,470 vs. 900 +/- 390%.s. The norepinephrine (NE) concentration required to increase PGE(2) and substance P release from isolated renal pelvises was 10 pM in HNa and 6,250 pM in LNa diet rats. In HNa diet pelvises 10 pM NE increased PGE(2) release from 67 +/- 6 to 150 +/- 13 pg/min and substance P release from 6.7 +/- 0.8 to 12.3 +/- 1.8 pg/min. In LNa diet pelvises 6,250 pM NE increased PGE(2) release from 64 +/- 5 to 129 +/- 22 pg/min and substance P release from 4.5 +/- 0.4 to 6.6 +/- 0.7 pg/min. In the renal pelvic wall, ETB-R are present on unmyelinated Schwann cells close to the afferent nerves and ETA-R on smooth muscle cells. ETA-receptor (R) protein expression in the renal pelvic wall is increased in LNa diet. In HNa diet, renal pelvic administration of the ETB-R antagonist BQ788 reduced ERSNA-induced increases in ARNA and NE-induced release of PGE(2) and substance P. In LNa diet, the ETA-R antagonist BQ123 enhanced ERSNA-induced increases in ARNA and NE-induced release of substance P without altering PGE(2) release. In conclusion, activation of ETB-R and ETA-R contributes to the enhanced and suppressed interaction between ERSNA and ARNA in conditions of HNa and LNa diet, respectively, suggesting a role for ET in the renal control of ERSNA that is dependent on dietary sodium.

Nox activity is the major source of superoxide formation in renal proximal resistance arteries from elderly patients. Acute vasoconstrictor responses to alpha1-adrenoreceptor activation and to endothelin-1 do not depend on superoxide formation, while endothelium-dependent vasodilation in intrarenal arteries is reactive oxygen species-dependent.

The aim of the present study was to test the hypothesis that elevation of prorenin in plasma is sufficient to induce cardiac fibrosis. Normotensive cyp1a1ren-2 transgenic rats with normal plasma prorenin and aldosterone levels were given 0.125% indole-3-carbinol (I3C) orally for a period of 12 wk. Plasma prorenin and aldosterone levels were determined in 4-wk intervals, and cardiac marker enzymes for hypertrophy, fibrosis, and oxidative stress as well as cardiac pathology were investigated. In I3C-treated cyp1a1 ren-2 transgenic rats, plasma prorenin concentrations were >100-fold elevated (≥7.1 ± 2.6 μg ANG I·ml−1·h−1 vs. ≤0.07 ± 0.1; P < 0.001), whereas active renin levels were suppressed (0.09 ± 0.02 vs. 0.2 ± 0.1; P < 0.05). Aldosterone concentrations were elevated three- to fourfold for a period of >4 wk (574 ± 51 vs. 160 ± 68 pg/ml; P < 0.01). After 12 wk of I3C, rats exhibited moderate cardiac hypertrophy (heart weight/body weight 2.5 ± 0.04 vs. 3.1 ± 0.1 mg/g; P < 0.01). There was a slight increase in mRNA contents of endothelin 1 (1.21 ± 0.08 vs. 0.75 ± 0.007; P < 0.001), NADP oxidase-2 (1.03 ± 0.006 vs. 0.76 ± 0.04; P < 0.001), transforming growth factor-β (0.99 ± 0.06 vs. 0.84 ± 0.04; P < 0.05), collagen type I (1.32 ± 0.32 vs. 0.94 ± 0.18; P < 0.05), and intercellular adhesion molecule-1 (1.12 ± 0.12 vs. 0.84 ± 0.08; P < 0.05). These genes are known to be stimulated by the renin-angiotensin system. There were no histological signs of fibrosis in the heart. We found that prorenin and aldosterone alone are not sufficient to induce considerable cardiac fibrosis in the absence of sodium load.

Kidney graft-specific MRP2 deficiency has mild effects on the renal excretion of some organic solutes under experimental conditions and induces a protein and gene expression pattern indicative of activated antioxidant defense mechanisms. This suggests that MRP2 is a determinant of the redox status in tubular epithelial cells and thus of the susceptibility to renal damage under conditions of treatment with multiple drugs and increased oxygen radical formation.

ET-1-induced vasoconstriction is more ROCK-dependent in renal than in nonrenal resistance arteries. SAR407899 causes a greater inhibition of ET-1-induced vasoconstriction in renal resistance arteries from ZDF rats and patients than Y27632. The greater efficacy in renal vessels may contribute to the higher antihypertensive potency of SAR407899 compared with Y27632.

The aim of the study was to elucidate relations between senescence and cytokinin oxidase/dehydrogenase (CKX, EC 1.4.3.18/1.5.99.12). Segments derived from first foliage leaves of Hordeum vulgare L. cv. Alexis were put with their bases into water and kept in darkness. Their senescence was characterized, e.g. by a 60% decline in chlorophyll within 5 days. During this time, the in vitro activity of CKX increased fast and markedly, e.g. 14‐fold. Application of 10−4M kinetin (Kin), which slightly retarded the loss of chlorophyll, multiplied the enhancement of CKX activity strongly. Both in the presence and in the absence of Kin, the proportion of glycosylated to non‐glycosylated CKX increased during senescence. By hybridization with an antisense RNA probe derived from a fragment of the CKX gene Zmckx1 of maize, an increase of the corresponding transcript of the barley gene Hvckx1 in segments incubated without Kin was shown. The content of base and riboside cytokinins slowly declined in such segments, which argues against triggering but for facilitating senescence processes by CKX.

(SHR). In SHR transplanted with a kidney from sympathectomized SHR, arterial pressure was lower and less Na ϩ sensitive than in SHR transplanted with a kidney from hydralazine-treated SHR. This study was performed to identify underlying renal mechanisms. Tests for differential renal mRNA expression of nine a priori selected genes revealed robust differences for renal medullary expression of the NADPH oxidase subunit p47phox . Therefore, we investigated the effects of neonatal sympathectomy on renal mRNA expression of NADPH oxidase subunits, NADPH oxidase activity, and renal function. In 10-wk-old sympathectomized SHR fed a 0.6% NaCl diet, medullary p47 phox and gp91 phox expression was 40% less than in hydralazine-treated SHR. Also, after a 1.8% NaCl diet, medullary p47 phox mRNA expression was lower in sympathectomized than in hydralazine-treated SHR. We found lower cortical (Ϫ30%, P Ͻ 0.01) and medullary (Ϫ30%, P Ͻ 0.05) NADPH oxidase activities in sympathectomized than in hydralazine-treated or untreated SHR. Glomerular filtration rate, renal blood flow, medullary blood flow, and fractional Na ϩ excretion in kidney grafts from sympathectomized and hydralazine-treated donors (n ϭ 8 per group) were similar at baseline and in response to a 20-mmHg rise in renal perfusion pressure. Renal vascular resistance was lower in kidneys from sympathectomized than hydralazine-treated donors (25 Ϯ 2 vs. 32 Ϯ 4 mmHg ⅐ min ⅐ ml Ϫ1 , P Ͻ 0.05). The results indicate that the sympathetic nervous system contributes to the level of renal NADPH oxidase activity and to perinatal programming of alterations in renal vascular function that lead to elevated renal vascular resistance in SHR. inbred strains; kidney; sympathetic activity; gene expression THE KIDNEY AND THE SYMPATHETIC nervous system contribute to the pathogenesis of arterial hypertension in spontaneously hypertensive rats (SHR) (12). Arterial pressure can be chronically lowered in SHR by neonatal sympathectomy (19,21), and renal mechanisms are involved in this chronic arterial pressure reduction (14). We previously showed lower arterial pressure in SHR transplanted with a kidney from a sympathectomized SHR donor than in SHR recipients of a kidney from a hydralazine-treated SHR donor (14). In addition, Na ϩ sensitivity of arterial pressure was lower in recipients of a kidney graft from sympathectomized donors than in recipients of a graft from hydralazine-treated donors (14). The present study was performed to identify mechanisms that may explain these findings; therefore, we focused on kidneys from sympathectomized and hydralazine-treated SHR. Limited data are available on chronic effects of neonatal sympathectomy on SHR kidneys. Thus we initially tested for differential mRNA expression of nine a priori selected genes in kidneys from sympathectomized and hydralazine-treated SHR exposed to three different experimental conditions. Our aim was to identify alterations in gene expression that persist under different conditions and, therefore, may be involved in chronic effects...