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Left renal nerves of rats were stimulated electrically to lower renal blood flow by 15, 30 and 45%, and the level of mRNA for renin and angiotensinogen were measured to evaluate the effect of short spells of nerve stimulation on renin and angiotensinogen expression within the kidney. While 1 hour stimulations led to a proportional decrease in sodium extraction and increase in plasma renin activity, stimulations for a longer period were required to enhance renal renin mRNA levels. A minimal enhancement of angiotensinogen mRNA level and low rates of nerve activity were observed.

This study examined the effect of leptin and orexin‐A on autonomic baroreflex control in conscious Wistar rats exposed to high‐fat (45% fat) or normal (3.4%) diet for 4 weeks. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored during the generation of baroreflex gain curves and acute volume expansion (VEP). Intracerebroventricular (ICV) leptin (1 μg/min) increased RSNA in the normal diet group (0.31 ± 0.04 vs 0.23 ± 0.03 mV/s) and MAP in the high‐fat diet group (115 ± 5 vs 105 ± 5 mm Hg, P <.05). Orexin‐A (50 ng/min) increased RSNA, HR and MAP in the high‐fat diet group (0.26 ± 0.03 vs 0.22 ± 0.02 mV/s, 454 ± 8 vs 417 ± 12 beats/min, 117 ± 1 vs 108 ± 1 mm Hg) and the normal diet group (0.18 ± 0.05 vs 0.17 ± 0.05 mV/s, 465 ± 10 vs 426 ± 6 beats/min, 116 ± 2 vs 104 ± 3 mm Hg). Baroreflex sensitivity for RSNA was increased during ICV leptin by 50% in the normal diet group, compared to 14% in the high‐fat diet group (P <.05). Similarly, orexin‐A increased baroreflex sensitivity by 56% and 50% in the high‐fat and normal diet groups, respectively (all P <.05). During ICV saline, VEP decreased RSNA by 31 ± 5% (P <.05) after 10 minutes and the magnitude of this response was blunted during ICV infusion of leptin (17 ± 2%, P <.05) but not orexin‐A in the normal diet group. RSNA response to VEP was not changed during ICV leptin or orexin‐A in the high‐fat diet group. These findings indicate possible central roles for leptin and orexin‐A in modulating the baroreflexes under normal or increased fat intake in conscious rats and potential therapeutic approaches for obesity associated hypertension. [ABSTRACT FROM AUTHOR]

Wu, Xiao Chun, Peter J. Harris, and Edward J. Johns. Nitric oxide and renal nerve-mediated proximal tubular reabsorption in normotensive and hypertensive rats. Am. J. Physiol. 277 (Renal Physiol. 46): F560-F566, 1999.--In Inactin-anesthetized Wistar rats with an intact renal innervation, intratubular nitro-L-arginine methyl ester (L-NAME, [10.sup.-4] M) increased proximal fluid uptake ([J.sub.va], at 2.47 [+ or -] 0.61 x [10.sup.-4] [mm.sup.3] [multiplied by] [mm.sup.-2] [multiplied by] [s.sup.-1]) by 17% (P [is less than] 0.05), whereas coadministration with sodium nitroprusside (SNP, [10.sup.-4] M) decreased [J.sub.va] by 18% (P [is less than] 0.01). Similar manipulation of NO generation was without effect in groups of Wistar rats subjected to acute renal denervation. Intratubular aminoguanidine ([10.sup.-4] M), a selective inducible nitric oxide synthase (NOS) blocker, had no effect on [J.sub.va] in intact kidneys of Wistar rats, but the neuronal NOS (nNOS) blocker, 7-nitroindazole ([10.sub.-4] M and [10.sup.-6] M) increased [J.sub.va] by 19-23% (both P [is less than] 0.001). In stroke-prone spontaneously hypertensive rats (SHRSP), [J.sub.va] values in the innervated kidneys were lower (P [is less than] 0.05) than in the corresponding Wistar groups and were unchanged by intratubular L-NAME or L-NAME plus SNP. The tonic attenuation of proximal epithelial transport by NO was dependent on the renal sympathetic nerves and appeared to be generated by the nNOS isoform of the enzyme. This role of NO was not evident in the SHRSP. nitric oxide synthase; renal sympathetic nerves; proximal tubular sodium reabsorption; stroke-prone spontaneously hypertensive rats

Left ventricular hypertrophy (LVH) is associated with decreased responsiveness of renal α1-adrenoreceptors subtypes to adrenergic agonists. Nitric oxide donors are known to have antihypertrophic effects however their impact on responsiveness of renal α1-adrenoreceptors subtypes is unknown. This study investigated the impact of nitric oxide (NO) and its potential interaction with the responsiveness of renal α1-adrenoreceptors subtypes to adrenergic stimulation in rats with left ventricular hypertrophy (LVH). This study also explored the impact of NO donor on CSE expression in normal and LVH kidney. LVH was induced using isoprenaline and caffeine in drinking water for 2 weeks while NO donor (L-arginine, 1.25g/Lin drinking water) was given for 5 weeks. Intrarenal noradrenaline, phenylephrine and methoxamine responses were determined in the absence and presence of selective α1-adrenoceptor antagonists, 5- methylurapidil (5-MeU), chloroethylclonidine (CeC) and BMY 7378. Renal cortical endothelial nitric oxide synthase mRNA was upregulated 7 fold while that of cystathione γ lyase was unaltered in the NO treated LVH rats (LVH-NO) group compared to LVH group. The responsiveness of renal α1A, α1B and α1D-adrenoceptors in the low dose and high dose phases of 5-MeU, CEC and BMY7378 to adrenergic agonists was increased along with cGMP in the kidney of LVH-NO group. These findings suggest that exogenous NO precursor up-regulated the renal eNOS/NO/cGMP pathway in LVH rats and resulted in augmented α1A, α1B and α1D adrenoreceptors responsiveness to the adrenergic agonists. There is a positive interaction between H2S and NO production in normal animals but this interaction appears absent in LVH animals. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Dietary sodium manipulation alters the magnitude of angiotensin-(1-7) [Ang-(1-7)]-induced natriuresis. The present study sought to determine whether this was related to relative changes in the activity of intrarenal Mas and/or AT1 receptors., What is the main finding and its importance? Angiotensin-(1-7)-induced diuresis and natriuresis is mediated by intrarenal Mas receptors. However, intrarenal AT1 receptor blockade also had an inhibitory effect on Ang-(1-7)-induced natriuresis and diuresis. Thus, Ang-(1-7)-induced increases in sodium and water excretion are dependent upon functional Mas and AT1 receptors., We investigated whether angiotensin-(1-7) [Ang-(1-7)]-induced renal haemodynamic and excretory actions were solely dependent upon intrarenal Mas receptor activation or required functional angiotensin II type 1 (AT1) receptors. The renin-angiotensin system was enhanced in anaesthetized rats by prior manipulation of dietary sodium intake. Angiotensin-(1-7) and AT1 and Mas receptor antagonists were infused into the kidney at the corticomedullary border. Mas receptor expression was measured in the kidney. Mean arterial pressure, urine flow and fractional sodium excretion were 93 ± 4 mmHg, 46.1 ± 15.7 μl min−1 kg−1 and 1.4 ± 0.3%, respectively, in the normal-sodium group and 91 ± 2 mmHg, 19.1 ± 3.3 μl min−1 kg−1 and 0.7 ± 0.2%, respectively, in the low-sodium group. Angiotensin-(1-7) infusion had no effect on mean arterial pressure in rats receiving a normal-sodium diet but decreased it by 4 ± 5% in rats receiving a low-sodium diet ( P < 0.05). Interstitial Ang-(1-7) infusion increased urine flow twofold and fractional sodium excretion threefold ( P < 0.05) in rats receiving a normal-sodium diet and to a greater extent, approximately three- and fourfold, respectively, in rats receiving the low-sodium diet (both P < 0.05). Angiotensin-(1-7)-induced increases in urine flow and fractional sodium excretion were absent in both dietary groups during intrarenal AT1 or Mas receptor inhibition after either losartan or A-779, respectively. Thus, AT1 receptor activation, as well as Mas receptor activation, plays an essential role in mediating Ang-(1-7)-induced natriuresis and diuresis. Whether this is because Ang-(1-7) partly antagonizes AT1 receptors or whether Ang-(1-7)-induced natriuresis is mediated through AT1-Mas receptor dimerization remains unclear. [ABSTRACT FROM AUTHOR]