Effects of specific COX-2-inhibition on renin release and renal and systemic prostanoid synthesis in healthy volunteers

Stichtenoth, Dirk O.; Marhauer, Verena; Tsikas, Dimitrios; Gutzki, Frank‐Mathias; Frölich, Jürgen C.

doi:10.1111/j.1523-1755.2005.00676.x

Cited by 56 publications

(45 citation statements)

References 40 publications

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“…To investigate the acute stimulatory arm of the macula densa mechanism in vivo, loop diuretics have been widely used to block NKCC2 transport activity in tubular and macula densa cells, thereby mimicking a low salt concentration at the macula densa. In accordance with the results of the studies in isolated JGAs, the stimulation of plasma renin in response to an acute administration of loop diuretics was markedly attenuated by a preceding blockade or genetic deletion of COX-2 in vivo [56,59,116]. Although this effect of systemic COX-2 blockade or deletion is not necessarily the result of reduced PGE2 formation in macula densa cells, it fits well with the macula densa control of renin release.…”

Section: The Macula Densa Mechanismsupporting

confidence: 86%

Salt feedback on the renin-angiotensin-aldosterone system

Schweda

2014

Pflugers Arch - Eur J Physiol

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The renin-angiotensin-aldosterone system (RAAS) is a central element in the control of the salt and water balance of the body and arterial blood pressure. The activity of the RAAS is controlled by the protease renin, which is released from renal juxtaglomerular epithelioid cells (JGE cells) into the circulation. Renin release is regulated by a complex interplay of several locally acting hormones or mechanisms and longer feedback loops one of which involves salt intake. Acute NaCl loads or longer lasting high salt intakes suppress plasma renin activity, whereas reductions in NaCl intake stimulate it. Because the activation of the RAAS conserves the salt content of the body, a classical feedback loop between salt intake/body salt content and renin is established. Despite of its important role for body fluid homeostasis, the precise signaling pathways connecting salt intake with the synthesis and release of renin are only incompletely understood. Four putative controllers of the salt-dependent regulation of the RAAS have been suggested: (1) the macula densa mechanism which adjusts renin release in response to changes in the renal tubular salt concentration; (2) salt-dependent changes in the arterial blood pressure; (3) circulating salt-dependent hormones, particularly the atrial natriuretic peptide (ANP); and (4) renal sympathetic nervous activity, which is regulated by extracellular volume and arterial blood pressure. In this review, the role of these known controllers of the RAAS will be discussed with special emphasis on their relative contributions to the salt-dependent regulation of the RAAS at different time frames.

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Section: The Macula Densa Mechanismsupporting

confidence: 86%

Salt feedback on the renin-angiotensin-aldosterone system

Schweda

2014

Pflugers Arch - Eur J Physiol

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“…In addition, stimulation of the renin system after the application of loop diuretics may be at least partly related to the enhanced vascular prostacyclin formation (518). Conversely, the attenuation of renin secretion in response to loop diuretics by inhibitors of cyclooxygenases appears to be partially mediated by the reduced vascular prostacylin synthesis (344,414,415,827).…”

Section: Prostanoidsmentioning

confidence: 99%

Physiology of Kidney Renin

Castrop

Höcherl

Kurtz

et al. 2010

Physiological Reviews

232

277

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The protease renin is the key enzyme of the renin-angiotensin-aldosterone cascade, which is relevant under both physiological and pathophysiological settings. The kidney is the only organ capable of releasing enzymatically active renin. Although the characteristic juxtaglomerular position is the best known site of renin generation, renin-producing cells in the kidney can vary in number and localization. (Pro)renin gene transcription in these cells is controlled by a number of transcription factors, among which CREB is the best characterized. Pro-renin is stored in vesicles, activated to renin, and then released upon demand. The release of renin is under the control of the cAMP (stimulatory) and Ca2+(inhibitory) signaling pathways. Meanwhile, a great number of intrarenally generated or systemically acting factors have been identified that control the renin secretion directly at the level of renin-producing cells, by activating either of the signaling pathways mentioned above. The broad spectrum of biological actions of (pro)renin is mediated by receptors for (pro)renin, angiotensin II and angiotensin-( 1 – 7 ).

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“…A possible explanation for the finding by Virdis et al 1 on involvement of COX-2-derived oxidative stress in essential hypertension may be that COX inhibitors act distinctly different on oxidative stress and PGI 2 and TxA 2 synthesis. In vivo in healthy humans, celecoxib (a COX-2 selective inhibitor) and indomethacin (a COX-unselective inhibitor) decreased oxidative stress ( Figure) and PGI 2 synthesis, 3 whereas indomethacin but not celecoxib inhibited TxA 2 synthesis. 3 Taken together, COX-2 inhibition by nonsteroidal anti-inflammatory drugs is associated with oxidative stress decrease but this does not translate into cardiovascular protection.…”

Section: To the Editormentioning

confidence: 99%

“…In vivo in healthy humans, celecoxib (a COX-2 selective inhibitor) and indomethacin (a COX-unselective inhibitor) decreased oxidative stress ( Figure) and PGI 2 synthesis, 3 whereas indomethacin but not celecoxib inhibited TxA 2 synthesis. 3 Taken together, COX-2 inhibition by nonsteroidal anti-inflammatory drugs is associated with oxidative stress decrease but this does not translate into cardiovascular protection. The cardiovascular risk of COX-unselective and selective COX-2 inhibitors is well established.…”

Section: To the Editormentioning

confidence: 99%

Endothelial Nitric Oxide Synthase, Cyclooxygenase-2, and Essential Hypertension: Is There an Interaction?

Tsikas

Stichtenoth

2013

Hypertension

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Nitric oxide (NO), prostacyclin (PGI 2 ), and thromboxane (TxA 2 ) are produced by NO synthase (NOS) and cyclooxygenase (ie, COX-1 and COX-2) isoforms, respectively. They are highly potent vasoactive molecules. NOS and COX pathways are assumed to interact and modulate each other. Both NOS and COX can produce superoxide which may react with NO to produce peroxynitrite (ONOO − ), thus diminishing NO bioactivity. Peroxynitrite may decrease NOS activity, but its action on COX is 2 sided; it may enhance or decrease COX activity depending on its concentration. Using experimental COX-1 and COX-2 selective inhibitors, Virdis et al 1 reported that in essential hypertension COX-2 decreased the bioavailability of endothelial NOS (eNOS)-derived NO and uncoupled eNOS in small arteries by increasing oxidative stress. In newly diagnosed mild uncomplicated patients with essential hypertension, we found that PGI 2 synthesis and oxidative stress are not altered compared with healthy normotensives, 2 whereas NO synthesis is slightly (27%) decreased, suggesting that NO biosynthesis but not NO bioavailability is diminished in essential hypertension. A possible explanation for the finding by Virdis et al 1 on involvement of COX-2-derived oxidative stress in essential hypertension may be that COX inhibitors act distinctly different on oxidative stress and PGI 2 and TxA 2 synthesis. In vivo in healthy humans, celecoxib (a COX-2 selective inhibitor) and indomethacin (a COX-unselective inhibitor) decreased oxidative stress ( Figure) and PGI 2 synthesis, 3 whereas indomethacin but not celecoxib inhibited TxA 2 synthesis. 3Taken together, COX-2 inhibition by nonsteroidal anti-inflammatory drugs is associated with oxidative stress decrease but this does not translate into cardiovascular protection. The cardiovascular risk of COX-unselective and selective COX-2 inhibitors is well established.

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Effects of specific COX-2-inhibition on renin release and renal and systemic prostanoid synthesis in healthy volunteers

Cited by 56 publications

References 40 publications

Salt feedback on the renin-angiotensin-aldosterone system

Salt feedback on the renin-angiotensin-aldosterone system

Physiology of Kidney Renin

Endothelial Nitric Oxide Synthase, Cyclooxygenase-2, and Essential Hypertension: Is There an Interaction?

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