The Effect of Isoprenaline Infusion on Renal Renin and Angiotensinogen Gene Expression in the Anaesthetised Rat

Abstract

In this study, we investigated the ability of acute infusions of isoprenaline to alter renin and angiotensinogen gene expression in the kidney of rats anaesthetised with chloralose‐urethane. Groups of rats received I.V. infusions of either saline or the β‐adrenoceptor agonist isoprenaline at 400 ng kg−1 min−1 for 4 h. The isoprenaline infusion caused a sustained decrease in mean blood pressure of approximately 20 mmHg (P < 0.01), an increase in heart rate of 50 beats min−1 (P < 0.01) and reductions in urine flow and sodium excretion of 80‐90% (both P < 0.01). Renal blood flow and glomerular filtration rate were transiently reduced by 21% (P < 0.01) and 61% (P < 0.001), respectively, in the first hour, recovering to baseline levels after 4 h of infusion. At the end of the study, plasma renin activity was raised approximately 6‐fold (P < 0.01) while renal renin and angiotensinogen mRNA levels were 1.8‐ and 1.5‐fold higher (both P < 0.05) compared to the control group (saline infusion). The isoprenaline‐induced renin secretion could have been mediated via the activation of β‐adrenoceptors resulting in the exocytosis of renin‐containing granules, with a smaller contribution being due to reduced renal haemodynamics. The increase in renal renin gene expression in response to isoprenaline was probably due primarily to the intracellular signalling processes acting directly on nuclear mechanisms. Similarly, the increased renal angiotensinogen gene expression most probably reflected a direct action of the isoprenaline. These findings provide evidence that catecholamines are involved in mechanisms that rapidly alter the expression of the genes of the renin‐angiotensin system within the kidney.

Regulation of Renin Release via Cyclic ADP-Ribose-Mediated Signaling: Evidence from Mice Lacking CD38 Gene

“…It has been reported that isoprenaline directly activates β-adrenoceptor on JG cells and stimulates adenylate cyclase to produce cAMP, which causes a cAMP-dependent protein kinase-A activation resulting in renin release [20]. In the present study, isoprenaline was found to increase the PRA by 3-fold in CD38 −/− mice, which was much higher compared to that observed in CD38 +/+ mice.…”

“…The surgery was performed as described previously [20–21]. In brief, after being fasted overnight the mice were anesthetized with ketamine (50 μg/g intraperioneally; Parke-Davis GmbH, Berlin, Germany) and inactin (100 μg/g intraperitoneally; Res Biochemical, Inc., Natick, MA) and then placed on a heated table for maintenance of body temperature at 37°C.…”

“…Isoprenaline infusion has been often used to stimulate renin release acutely [20]. To perform these experiments, mice were divided into 4 groups (n=8 in each group) including CD38 +/+ mice with or without i.v.…”

Physiology of Kidney Renin

“…JG cells contain ␤ 1 -adrenergic receptors (81,161). The systemic application of the ␤-adrenoreceptor agonist isoproterenol by chronic infusion into rats, both time and dose dependently, stimulates the synthesis and secretion of renin (355,598,802). In addition, isoproterenol infusion increased renin mRNA expression and PRA in rats during normal and high salt intake, but not during low salt intake (355).…”

Acquired Unilateral Melanocytic Nevi in Otherwise Normal Skin

“…A histopathological change in PUL is a typical lentigo simplex that shows an increase in nevoid melanocytes in the basal layer of the epidermis. In a rare occasion, PUL has been reported to show a histological finding of ‘lentigo’ with a small cluster of a nevomelanocytic nest in the basal layer [7]. In the present case, histopathology of the biopsy specimen revealed a typical compound-type nevus.…”