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

Wang, Junling; Cheng, Hao; Harris, Raymond C.

doi:10.1161/01.hyp.34.1.96

Cited by 169 publications

(145 citation statements)

References 40 publications

(57 reference statements)

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“…Renin inhibition can be triggered by simultaneous use of cyclooxygenase inhibitors (nonsteroidal anti-inflammatory drugs; NSAIDs), leading to hyperkalemia and metabolic hyperchloremic acidosis [73,74]. Heparin impairs aldosterone synthesis as a result of direct toxicity to the zona glomerulosa, with inhibition of aldosterone synthase (adrenal 18-hydroxylase).…”

Section: Inhibition Of the Aldosterone Axis (Angiotensin Inhibition Amentioning

confidence: 99%

Drug-induced acid-base disorders

et al. 2014

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The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal antiinflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g

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Section: Inhibition Of the Aldosterone Axis (Angiotensin Inhibition Amentioning

confidence: 99%

Drug-induced acid-base disorders

et al. 2014

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“…In contrast to Cox-1, differences exist in the expression pattern of Cox-2 between different species. In the renal cortex of rat, rabbit, and dog, Cox-2 has been reported to be expressed in the macula densa and surrounding cells of the thick ascending limb of Henle (13)(14)(15)(16)(17)(18)(19), whereas glomerular podocytes and blood vessels appear as the major sites of expression in the cortex of the kidney of humans and monkeys (13,15). In the medulla of the rat, Cox-2 is expressed in interstitial cells and at lower levels in the collecting ducts (13,15).…”

mentioning

confidence: 99%

“…Thus, Cox-2 expression in the macula densa and surrounding cells of the cTALH has been reported to be increased by a low-salt diet (14), by inhibition of the renin-angiotensin system (16,17), by renal hypoperfusion (18), or by furosemide treatment (19). A high-salt diet on the other hand has been shown to reduce Cox-2 expression in the kidney cortex (20,21).…”

mentioning

confidence: 99%

Low Tonicity Mediates a Downregulation of Cyclooxygenase-1 Expression by Furosemide in the Rat Renal Papilla

Castrop¹,

Vitzthum²,

Schumacher³

et al. 2002

Journal of the American Society of Nephrology

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Abstract. It is well known that loop diuretics enhance the renal excretion of prostanoids; therefore, this study aimed to characterize the influence of loop diuretics on the intrarenal expression of cyclooxygenases, which are the key enzymes for prostanoid formation. Male Sprague-Dawley rats were infused with furosemide (12 mg/kg per d) for 6 d, and the expression of cyclooxygenase-1 and -2 (Cox-1 and Cox-2) was analyzed in the different kidney zones. Furosemide increased Cox-2 mRNA expression approximately twofold in the cortex, but it left Cox-1 mRNA expression unaltered there. In the outer medulla, furosemide changed neither Cox-1 nor Cox-2 mRNA expression. In the inner medulla, however, furosemide decreased Cox-1 and Cox-2 mRNA levels to approximately 30% and 60% of their control levels, respectively. The downregulation of mRNA was paralleled by a decrease of Cox protein in the collecting ducts and interstitial cells. Moreover, tissue prostaglandin E 2 (PGE 2 ) concentrations in the papilla were markedly decreased by furosemide to about 30% of the control level. Furosemide lowered urine osmolality from 1550 mosmol/kg to 480 mosmol/ kg; therefore, further consideration was given to the influence of tonicity as a possible mediator of the effects of furosemide on the Cox expression. Water loading was therefore used to reduce the medullary tonicity by a second maneuver. Water loading led to a similar reduction in papillary Cox mRNA expression and PGE 2 content like furosemide. To investigate the influence of the osmolarity on the expression of Cox and the production of PGE 2 under defined in vitro conditions, inner medullary collecting duct cells were incubated with culture medium containing graded amounts of NaCl ranging from 200 mmol/L to 600 mmol/L, and Cox-1 and Cox-2 mRNA abundance were determined after 24 h an 48 h. Cox-1 and Cox-2 mRNA abundance changed in parallel with the osmolarity. The data suggest that loop diuretics decrease the expression of cyclooxygenases and consequently tissue PGE 2 concentrations in the kidney inner medulla. This effect could be related to the breakdown of the papillary osmotic gradient induced by loop diuretics.

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“…The effects of NSAIDs on blood pressure have been investigated in several experimental trials and in heterogeneous populations 18,19 . COX-2-derived prostanoids such as PGE-2 and PGI-2, which act on renal tubules and ducts and on the macula densa, respectively, modulate the resorption of sodium and water and stimulate the production and release of renin, which acts as a potent systemic and renal vasoconstrictor 3,20 .…”

Section: Discussionmentioning

confidence: 99%

Parecoxib reduces renal injury in an ischemia/reperfusion model in rats

et al. 2015

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PURPOSE:To evaluate the effect of parecoxib (an NSAID) on renal function by measuring plasma NGAL (serum neutrophil gelatinaseassociated lipocalin) levels in an induced-ischemia rat model. METHODS:Forty male Wistar rats were randomly assigned to one of four groups: Ischemia (I), Ischemia/parecoxib (IP), No-ischemia (NI), and No-ischemia/parecoxib (NIP). Body weight, mean arterial pressure, heart rate, body temperature, NGAL levels, and renal histology were compared across groups. RESULTS:The Ischemia (I) group, which did not receive parecoxib, showed the highest NGAL levels (p=0.001), while the IP group, which received the medication, had NGAL levels similar to those of the non-ischemic (NI and NIP) groups. CONCLUSION:Parecoxib resulted in renal protection in this experimental model.

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

Cited by 169 publications

References 40 publications

Drug-induced acid-base disorders

Drug-induced acid-base disorders

Low Tonicity Mediates a Downregulation of Cyclooxygenase-1 Expression by Furosemide in the Rat Renal Papilla

Parecoxib reduces renal injury in an ischemia/reperfusion model in rats

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