Neonatal sympathectomy reduces NADPH oxidase activity and vascular resistance in spontaneously hypertensive rat kidneys

Abstract

(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...

Redox Control of Renal Function and Hypertension

“…Indeed, a few studies demonstrated no or very little expression of the regulatory subunits in the medulla. However, one report shows that, in SHRs, the expression of Nox1, Nox2, and p67 phox is higher in the renal medulla as compared with the cortex, and the expression of Nox4 and p22 phox is higher in the cortex than in the medulla (291). Per this group, the expression of p47 is about the same in the cortex versus medulla.…”

Amiloride lowers arterial pressure in cyp1a1ren-2 transgenic rats without affecting renal vascular function

“…For radiotelemetric measurements of arterial pressure and heart rate telemetric devices (TA11PA-C40, DSITransoma Medical, St Paul, Minnesota, USA) were implanted in 12-week-old rats as outlined previously [13,16]. Animals were allowed to recover for 10 days after transmitter implantation until the experiments were started.…”

Impaired coronary function in Wistar Ottawa Karlsburg W rats—a new model of the metabolic syndrome

“…Arterial pressure recordings Animals were implanted with telemetric arterial pressure recording devices (TA11PA-C40, Data Sciences International, St. Paul, MN, USA) at 8 months of age as previously described [9,27]. Recordings were performed over 24 h at 10 and 14 months of age.…”

“…Recordings were performed over 24 h at 10 and 14 months of age. Data were acquired with Dataquest Labpro 3.11 software (Data Sciences International) as reported in detail previously [9,27]. In 3-monthold ZDF rats, arterial pressure was measured with the animals freely moving in their home cages via a femoral artery catheter implanted 48 h before the recordings.…”

“…For determinations of creatinine clearance and urinary protein excretion, the animals were housed in metabolism cages as reported elsewhere [9,27]. While in metabolism cages, the rats had access to standard rat food and tap water ad libitum.…”