Role of the macula densa in the control of renal renin gene expression in two-kidney/one-clip rats

Schricker, K. Th.; Hamann, Marlies; Kaissling, Brigitte; Kurtz, Armin

doi:10.1007/bf00585940

Cited by 20 publications

(15 citation statements)

References 24 publications

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“…On the other hand, it would also be conceivable that activation of renin gene expression by amlodipine would not be susceptible to contralateral suppression to the same dose as in 2kidney-lcip rats without additional treatment. The reason for such a resistance to renin gene suppression is not yet clear, but in previous experiments we have observed that inhibition of renin gene expression in the contralateral kidneys was less pronounced in 2kidney-lclip rats when the renin system was stimulated by additional treatment, for example, with furosemide (Schricker et al, 1994a) or converting enzyme inhibitors (Schricker et al, 1994b).…”

Section: Discussionmentioning

confidence: 90%

Effect of amlodipine on renin secretion and renin gene expression in rats

Schricker

Hamann

Macher

et al. 1996

British J Pharmacology

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1 This study was done to characterize the influence of calcium channel blockade on renin secretion and renin gene expression in normal rats and rats with renovascular hypertension. To this end we studied the effects of the 1,4-dihydropyridine derivative, amlodipine, on plasma renin activity and renal renin m-RNA levels in normal rats and rats with unilateral renal hypoperfusion induced by applying 0.2 mm left renal artery clips over four days. 2 In normotensive rats, amlodipine significantly decreased basal blood pressure by about 20 mmHg when applied in a concentration of 5, 15 and 45 mg kg-'. Plasma renin activity and also renin mRNA levels were not changed after application of 5 mg kg-' of amlodipine. However, at a concentration of 15 or 45 mg kg-', amlodipine, significantly increased not only plasma renin activity by about 250% and 300%, but also renin mRNA levels by about 100% and 500%. The action of amlodipine on all these parameters was maximal after 24 h. Treatment with amlodipine in a concentration of 15 mg kg-' also increased renin immunoreactive areas in the kidney cortex by retrograde recruitment of renin expressing cells in the afferent arterioles. 3 In 2kidney-1 clip rats, systolic blood pressure rose continuously whilst plasma renin activity and renin m-RNA in the clipped kidney increased transiently and renin m-RNA in the contralateral kidney was constantly suppressed. Amlodipine at a concentration of 15 mg kg-' markedly attenuated the increase of blood pressure in 2kidney-1 clip rats, produced an almost additive effect on plasma renin activity and showed a tendency to increase renin m-RNA levels in the clipped kidneys. Renin m-RNA levels in the contralateral kidney were also significantly suppressed in the animals receiving additional treatment with amlodipine. 4 These findings suggest that inhibition of calcium channels by amlodipine stimulates renin secretion and renin gene expression in vivo. These stimulatory effects are almost additive to the changes of renin secretion occurring after an unilateral fall of renal perfusion pressure.

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Section: Discussionmentioning

confidence: 90%

Effect of amlodipine on renin secretion and renin gene expression in rats

Schricker

Hamann

Macher

et al. 1996

British J Pharmacology

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“…Under physiological conditions, glomerular filtration rate and absolute proximal reabsorption are dependent on, and reflections of, effective circulating volume, and the macula densa is situated to serve as both a sensor and an effector of total salt and volume homeostasis; however, pathophysiological decreases in renal blood flow secondary to renal artery stenosis may also be sensed by the macula densa as a decrease in effective circulating volume. Although the underlying mechanisms for the elevated renin activity in these states were previously attributed solely to baroreceptor activation of renin, 1 recent studies by Kurtz and associates 7,8 have shown that macula densa-mediated renin release is also involved in mediating the increased renin expression in the 2-kidney, 1 clip model of RVH. In addition, these investigators have demonstrated an important role for prostanoids in mediating the increased renin expression in this model.…”

Section: Discussionmentioning

confidence: 99%

“…However, more recent studies have suggested that macula densa signaling may also contribute to increased renin production in RVH. 7,8 The conversion of arachidonic acid to prostaglandin H 2 by prostaglandin G 2 /H 2 synthase (cyclooxygenase) is a key enzymatic step in the regulation of prostaglandin synthesis. 9 Two isoforms of cyclooxygenase (COX) exist: constitutive (COX-1) and inducible (COX-2).…”

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Cyclooxygenase-2 Inhibition Decreases Renin Content and Lowers Blood Pressure in a Model of Renovascular Hypertension

1999

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Abstract-It has been proposed that the macula densa participates in the regulation of increased renin expression in renovascular hypertension (RVH) and that prostaglandins may be among the mediators of macula densa function. We have previously shown that in renal cortex, cyclooxygenase-2 (COX-2) expression is localized to the macula densa and surrounding cortical thick ascending limb and increases in high-renin states, such as salt restriction and angiotensinconverting enzyme inhibition. In the present studies, we examined the effect of the selective COX-2 inhibitor SC58236 on plasma renin activity (PRA) and renal renin expression in RVH in rats. The aorta was coarcted between right and left renal arteries, and animals received either SC58236 or vehicle for 1 week. At day 8, vehicle-treated coarcted rats were hypertensive (mean carotid arterial blood pressure: 138Ϯ3 versus 87Ϯ2 mm Hg in sham-operated controls; nϭ9 to 11; PϽ0.001) and exhibited a disparity of kidney size (ratio left/right kidney: 0.78Ϯ0.04 versus 1.02Ϯ0.02; nϭ9 to 10; PϽ0.001). PRA increased significantly (84.6Ϯ6.5 versus 9.0Ϯ1.4 ng angiotensin I [Ang I] per milliliter per hour; nϭ8 to 9; PϽ0.01). In the coarcted rats, neither renin mRNA expression nor renin activity of the right kidney was altered (renin/GAPDH mRNA: 1.12Ϯ0.05-fold levels in control rats; nϭ6; PϭNS; renin activity: 23.4Ϯ1.8 versus 27.1Ϯ3.4 ng Ang I per hour per milligram protein; nϭ8 to 9; PϭNS). However, the renin mRNA of the left kidney increased to 3.0Ϯ0.6-fold of control (nϭ6), and the renin activity increased to 189.0Ϯ28.6 ng Ang I per hour per milligram protein (nϭ8; PϽ0.01). Expression of COX-2 mRNA and immunoreactive protein increased in the affected left kidney but was not different from control in the unaffected right kidney. SC58236 treatment to coarcted rats did not affect kidney size (ratio left/right kidney: 0.79Ϯ0.06; nϭ9). However, PRA was significantly decreased compared with the vehicle-treated coarcted rats (19.8Ϯ2.8 ng Ang I per milliliter per hour; nϭ9; PϽ0.01). The left kidney renin mRNA and renin content were also decreased (1.7Ϯ0.3-fold control; nϭ6; PϽ0.05; and 45.7Ϯ7.6 ng Ang I per hour per milligram protein; nϭ9; PϽ0.01, respectively), while renin mRNA and renin content of the right kidney were not altered. SC58236 lowered mean arterial blood pressure (122Ϯ5 mm Hg; nϭ14; PϽ0.05 compared with vehicle). A significant correlation was observed between PRA and mean blood pressure (rϭ0.75; PϽ0.01). In summary, these studies indicate that the selective COX-2 inhibitor SC58236 decreases renin production and release in RVH and suggest an important role for COX-2 regulation of the renin-angiotensin system. (Hypertension. 1999;34:96-101.)Key Words: renin Ⅲ cyclooxygenase Ⅲ hypertension, renal Ⅲ macula densa Ⅲ kidney B oth experimental models and clinical experience have indicated that prostaglandins are involved in the regulation of renal renin expression and release. [1][2][3][4] In addition to physiological regulation of renin in response to alterations in intr...

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“…[2][3][4][5] Moreover, several studies suggested that the cyclooxygenase products prostaglandin E2 and prostacyclin are involved in the renal baroreceptor mechanism. 6 -10 However, because blockade of prostaglandin formation did not attenuate the pressure dependent regulation of the renin system in other investigations, [11][12][13][14] the precise role of prostanoids in the renal baroreceptor mechanism is not entirely clear.…”

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Blood Pressure–Dependent Inhibition of Renin Secretion Requires A1 Adenosine Receptors

et al. 2005

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Abstract-Renal perfusion pressure (RPP) regulates renin release with a reduction of RPP stimulating and an elevation inhibiting renin secretion. The precise sensing and effector mechanisms by which changes in arterial pressure are linked to the exocytosis of renin are not well-defined. The present experiments were designed to study the potential role of adenosine as a mediator of this renal baroreceptor mechanism. In isolated perfused mouse kidneys a stepwise reduction of RPP from 90 mm Hg to 65 and 40 mm Hg stimulated renin secretion rates (RSR) 1.4-fold and 3.6-fold, whereas stepwise elevations of RPP from 90 mm Hg to 115 and 140mm Hg suppressed RSR to 64% or 40% of baseline. Inactivation of A1 adenosine receptors by either pharmacological blockade (DPCPX 1mol/L) or genetic deletion (A1AR Ϫ/Ϫ mice) did not modify the stimulation of renin release by a low RPP, but completely prevented the suppression of renin secretion by higher perfusion pressures. In vivo, the induction of arterial hypertension by either acute (single subcutaneous injection) or chronic (osmotic minipump for 72 hours) application of phenylephrine significantly reduced plasma renin concentration (PRC) in wild-type mice to Ϸ40% of control, whereas it did not significantly affect PRC in A1ARϪ/Ϫ mice. Together these data demonstrate that A1 adenosine receptors are indispensable for the inhibition of renin secretion by an increase in blood pressure, suggesting that formation and action of adenosine is responsible for baroreceptor-mediated inhibition of renin release. In contrast, the stimulation of the renin system by a low blood pressure appears to follow different pathways.

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Role of the macula densa in the control of renal renin gene expression in two-kidney/one-clip rats

Cited by 20 publications

References 24 publications

Effect of amlodipine on renin secretion and renin gene expression in rats

Effect of amlodipine on renin secretion and renin gene expression in rats

Cyclooxygenase-2 Inhibition Decreases Renin Content and Lowers Blood Pressure in a Model of Renovascular Hypertension

Blood Pressure–Dependent Inhibition of Renin Secretion Requires A1 Adenosine Receptors

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