Armin Kurtz

Role of Renal Nerves in the Stimulation of the Renin System by Reduced Renal Arterial Pressure

The aim of this study was to determine the role of renal innervation in the prolonged stimulation of renin secretion and renin synthesis accompanying renal artery stenosis. Male Sprague-Dawley rats, in which the left kidney had been denervated or sham denervated 4 days earlier, received a left renal artery clip (ID 0.2 mm). Plasma renin activity and renin mRNA were assayed 1, 2, or 4 days after clipping. The stimulation of both plasma renin activity and renin mRNA was blunted markedly in the rats with the denervated clipped kidney. The typical suppression of renin mRNA in the intact right kidney, however, was not different between rats with sham-denervated or denervated left kidneys, nor was the increase of blood pressure in response to renal artery clipping different between the experimental groups. To test whether the suppression of renin mRNA in the contralateral kidney was related to the increase of blood pressure, another group of rats with denervated clipped left kidneys was treated additionally with the T-type calcium channel blocker mibefradil (15 mg. kg(-1). d(-1)). Despite blood pressure normalization by mibefradil, plasma renin activities and renin mRNA levels in the clipped denervated kidneys and in the intact right kidneys remained unchanged. These findings suggest that renal nerves are responsible for marked background stimulation of both renin secretion and renin mRNA expression, which is normally masked by the inhibitory effect of renal perfusion pressure on the renin system. Renal nerve activity is therefore an important determinant of the gain of renin stimulation during reduced renal arterial pressure.

The role of angiotensin II in the feedback control of renin gene expression.

Abstract This study aimed to characterize the influence of endogenous angiotensin II on renal renin gene expression during different states of a stimulated and of a suppressed renin system. To this end the renin system in male Sprague Dawley rats was stimulated by unilateral renal artery clipping (0.2 mm clip), by furosemide (60 mg/kg per diem) or isoproterenol (160 μg/kg per diem), and by ingestion of a low-salt diet (0.02%), or was suppressed by setting a contralateral renal artery clip (0.2-mm clip) or by ingestion of a high-salt diet (4%). During the last 2 days of these different treatment regimens, the animals were treated with the angiotensin II AT1 receptor antagonist losartan (40 mg/kg per diem) and renal renin mRNA levels were assayed. Renin gene expression was stimulated four- to fivefold by renal artery clipping and isoproterenol infusion, two- to threefold by furosemide and a low-salt diet, and about fourfold by losartan. Additional treatment with losartan potentiated the stimulatory effects of a low-salt diet, of furosemide and of isoproterenol infusion on renin gene expression, whilst there was no significant additional effect of losartan on renin gene expression in clipped kidneys. Both contralateral renal artery clipping and a high-salt diet decreased renin mRNA levels to about 50% of the control value. In rats with a unilateral clip, additional losartan treatment caused renin mRNA to increase to about 350% of the control value in the contralateral kidney but to only 110% of the control value in animals on a high-salt diet. These findings suggest that the enhanced formation of angiotensin II during a low-salt intake, during tubular inhibition of salt reabsorption or during β-adrenoreceptor activation plays a relevant negative feedback role in the activation of the renin gene. Moreover, in rats with one hypoperfused kidney, angiotensin II could be involved in the inhibition of renin gene expression in the contralateral kidney. In hypoperfused kidneys, however, and in animals on a high-salt diet, angiotensin II appears to play only a minor feedback role in the regulation of the renin gene.

In vivo carbon monoxide exposure and hypoxic hypoxia stimulate immediate early gene expression

Abstract This study aimed to examine the influence of acute tissue hypoxygenation on the expression of immediate early genes in different rat tissues. To this end male Sprague-Dawley rats were exposed to 0.1% carbon monoxide for 0.5, 1 and 6 h or to 9% oxygen for 6 h and mRNA levels for c-jun, c-fos, c-myc and EGR-1 were assayed by RNase protection in hearts, kidneys, livers and lungs. We found that hypoxia increased c-jun mRNA levels between twofold (lung) and eightfold (liver) in all organs examined; c-fos mRNA increased between threefold (lung) and 20-fold (heart); c-myc mRNA increased between twofold (lung) and sixfold (heart); and EGR-1 mRNA increased between twofold (lung) and sixfold (heart). Our findings suggest that acute tissue hypoxygenation is a general stimulus of the expression of immediate early genes in vivo. With regard to the sensitivity to hypoxia, organ differences appear to exist in that the lung is rather insensitive, whilst the heart is rather sensitive.