Role of prostanoids in regulation of the renin-angiotensin-aldosterone system by salt intake

Höcherl, Klaus; Kammerl, Martin C.; Schumacher, Karl; Endemann, D.H.; Grobecker, H.; Kurtz, Armin

doi:10.1152/ajprenal.00347.2001

Cited by 43 publications

(40 citation statements)

References 40 publications

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“…On the other hand, an up to 3-wk treatment with the COX-2 inhibitor rofecoxib did not alter renin mRNA or plasma renin activity in rats (14,15). A striking difference between these and the present studies is the marked upregulation of COX-2 expression in the rofecoxib-treated rats (14). It is possible that the pharmacological approach may not abolish local PG production, either because of accessibility problems or because the upregulated COX-2 expression enhances enzyme capacity that, in part, compensates for reduced enzyme activity.…”

Section: Discussionmentioning

confidence: 76%

“…The COX-2 inhibitor SC-58125 has been found to reduce plasma renin activity and renal renin mRNA levels in low salt-fed and renal hypertensive mice (9). On the other hand, an up to 3-wk treatment with the COX-2 inhibitor rofecoxib did not alter renin mRNA or plasma renin activity in rats (14,15). A striking difference between these and the present studies is the marked upregulation of COX-2 expression in the rofecoxib-treated rats (14).…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice

Kim¹,

Chen²,

Mizel³

et al. 2007

American Journal of Physiology-Renal Physiology

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.-In the current experiments, we determined the response of plasma renin concentration (PRC) to acute intraperitoneal administration of furosemide (40 mg/kg), hydralazine (2 mg/kg), isoproterenol (10 mg/kg), candesartan (50 g), or quinaprilate (50 g) in conscious wild-type (WT) and cyclooxygenase (COX)-2Ϫ/Ϫ mice on three different genetic backgrounds (mixed, C57BL/6, 129J). PRC was measured in plasma obtained by tail vein puncture. Basal PRC was significantly lower in COX-2Ϫ/Ϫ than WT mice independent of genetic background (51, 10, and 17% of WT in mixed, 129J, and C57BL/6). All five acute interventions caused significant increases of PRC in both COX-2ϩ/ϩ and Ϫ/Ϫ mice, but the response was consistently less in COX-2-deficient mice (e.g., ⌬PRC in ng ANG I ⅐ ml Ϫ1 ⅐ h Ϫ1 caused by furosemide, isoproterenol, hydralazine, quinaprilate, or candesartan 4,699 Ϯ 544, 3,534 Ϯ 957, 2,522 Ϯ 369, 9,453 Ϯ 1,705, 66,455 Ϯ 21,938 in 129J WT, and 201 Ϯ 78, 869 Ϯ 275, 140 Ϯ 71, 902 Ϯ 304, 2,660 Ϯ 954 in 129J COX-2Ϫ/Ϫ). A low-NaCl diet and enalapril for 1 wk caused a 14-fold elevation of PRC in COX-2Ϫ/Ϫ mice and was associated with a greatly increased PRC response to acute furosemide (⌬PRC 201 Ϯ 78 before and 15,984 Ϯ 2,397 after low Na/enalapril). As measured by radiotelemetry, blood pressure and heart rate responses to furosemide, hydralazine, isoproterenol, candesartan, or quinaprilate were not different between COX-2 genotypes. In conclusion, chronic absence of COX-2 reduces renin expression, release, and PRC and is associated with a reduced ability to alter PRC during acute stimulation regardless of the nature of the stimulus. COX-2 activity does not appear to be a mandatory and specific requirement for furosemide-stimulated renin secretion.furosemide; hydralazine; isoproterenol; quinaprilate; candesartan; genetic background; cyclooxygenase-2 INCREASES OR DECREASES OF NaCl concentration in the tubular fluid at the level of the macula densa are followed by inverse changes in the amount of renin released from juxtaglomerular cell stores, an event that is followed by changes in plasma renin concentration (PRC) and ANG II formation rate. Prostaglandins, specifically PGE 2 and PGI 2 , are known regulators of renin release, and they have been implicated in macula densamediated regulation of renin release (12). There is considerable support for the notion that PGE 2 is generated in macula densa cells through the action of cyclooxygenase (COX)-2 and that it is released when NaCl concentration at the macula densa is acutely reduced (20). In addition to the response of renin release to acute luminal NaCl perturbations, prolonged deviations of NaCl concentration at the macula densa are also believed to cause alterations in renin gene expression and renal renin content. For example, administration of a high-salt diet or chronic infusion of loop diuretics causes changes in renin mRNA and renal renin content that subsequently lead to changes of PRC. It is likely that prostaglandins are also involved in this up-or downregulation of renin e...

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 98%

Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice

Kim¹,

Chen²,

Mizel³

et al. 2007

American Journal of Physiology-Renal Physiology

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“…celecoxib, or nimesulide, attenuate an increase in renin secretion and renin expression in response to renovascular hypertension (8,14,25,28,37), low salt intake (8,16,18,29,38), and angiotensin II inhibition (5, 6, 19). It has been suggested that this striking difference between the various COX-2 inhibitors may be due to a lower accessibility of rofecoxib or celecoxib at the level of macula densa cells and/or the juxtaglomerular apparatus, which may lead to insufficiently high enough drug levels for a complete inhibition of local prostaglandin production (23).…”

Section: Discussionmentioning

confidence: 99%

“…However, studies with COX-2-deficient mice and with selective COX-2 inhibitors produced conflicting findings. It has been found that pharmacological inhibition of COX-2 with SC-58236 and SC-58125 as well as COX-2 deficiency attenuate the increase in renin release and renin expression due to renovascular hypertension, low salt intake, and angiotensin II inhibition (5,6,8,37,38), whereas commercially available COX-2 inhibitors, like rofecoxib and celecoxib, did not affect the stimulation of the renin system in response to these stimuli (14,18,19,25,28,29). Recently, it has been reported that COX-2 deficiency reduces basal renin expression and renin release but does not attenuate the secretion of renin in response to acute stimuli (23).…”

mentioning

confidence: 99%

COX-2 activity determines the level of renin expression but is dispensable for acute upregulation of renin expression in rat kidneys

Matzdorf¹,

Kurtz²,

Höcherl³

2007

American Journal of Physiology-Renal Physiology

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Matzdorf C, Kurtz A, Hö cherl K. COX-2 activity determines the level of renin expression but is dispensable for acute upregulation of renin expression in rat kidneys. Am J Physiol Renal Physiol 292: F1782-F1790, 2007. First published March 20, 2007; doi:10.1152/ajprenal.00513.2006.-The role of cyclooxygenase 2 (COX-2) in the control of renin is still a matter of debate, since studies with COX-2-deficient mice or with COX-2 inhibitors produced conflicting findings. Therefore, we studied the effect of the COX-2 inhibitor SC-58236 on the regulation of the renin system in adult rat kidneys. Renocortical tissue levels and urinary excretion of PGE2 were reduced to 65 and 40% of control values, respectively, after a single gavage of SC-58236 and did not further decrease on prolonged treatment. Plasma renin activity (PRA) and renin mRNA levels began to decrease after 3 days and reached a constant level of ϳ60% of control values after 5 days of treatment. Isoproterenol or left renal artery clipping for 2 days increased PRA and renin mRNA to similar levels in both vehicle-and SC-58236-treated rats after 2 days. Pretreatment with SC-58236 for 5 days, however, reduced the absolute increase in PRA and renin mRNA levels. Notably, the relative increases were not different between vehicle-and SC-58236-treated rats. Similar findings were observed for the stimulation of the renin system by angiotensin II inhibition and low salt intake. These findings indicate that COX-2 inhibition attenuates renin secretion and renin gene expression stimulated by a variety of parameters in proportion to the lowering of basal renin activity, while it does not interfere with the different stimulatory mechanism per se. As a consequence, it appears as if COX-2 activity relevantly determines the set point of the activity of the renin system in rat kidneys. SC-58236; renovascular hypertension; prostaglandins; cyclooxygenase; isoproterenol THE CONVERSION OF ARACHIDONIC acid to prostaglandin (PG) H 2 by cyclooxygenase (COX) is a key enzymatic step in the regulation of prostaglandin synthesis. Two isoforms of COX have been identified: a constitutive (COX-1) and an inducible (COX-2) form. COX-1 is the predominant isoform in the mammalian kidney and has been localized to arteries, glomeruli, and collecting ducts. COX-2 has been localized to arteries, collecting ducts, interstitial cells, cortical thick ascending limb of Henle (cTALH) cells, and macula densa cells. Prostaglandins have a major impact on kidney function. They are involved in the control of renal blood flow, glomerular filtration, salt excretion, and in the secretion and expression of renin (22).The renin-angiotensin system (RAS) plays a crucial role in the control of systemic blood pressure and in the control of salt and water balance (11). The formation and particularly the release of renin is the rate-limiting step within the RAS. Activation of the RAS increases and depression of the RAS lowers blood pressure and, as part of a negative feedback control, blood pressure in turn affects the s...

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“…Evidence from studies with spontaneously hypertensive rats using indomethacin and PGH 2 /TXA 2 receptor blockers (e.g., SQ 29,548) indicate that endothelium-derived PGH 2 and TXA 2 are contractile factors in intrarenal arteries that may underlie impaired relaxation to ACh (Dai et al, 1992;FuXiang et al, 1992). Numerous studies have addressed the role of prostaglandins during changes in dietary sodium (Hocherl et al, 2002), but the impact on small vessels is less well known. In the present study, indomethacin also partially restored ACh induced relaxation of renal arteries of lisinopril treated rats during low sodium.…”

Section: Discussionmentioning

confidence: 99%

Low Sodium Modifies the Vascular Effects of Angiotensin-Converting Enzyme Inhibitor Therapy in Healthy Rats

Kocks

Gschwend²,

Zeeuw

et al. 2004

J Pharmacol Exp Ther

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Low dietary sodium (LS) increases the effect of angiotensinconverting enzyme (ACE) inhibitor therapy in patients and experimental models, but mechanisms underlying this enhanced efficacy are largely unknown. Because the benefits of ACE inhibition are mediated to a considerable extent by their effect on the vasculature, we studied whether low sodium alters the vascular effects of ACE inhibition. Baseline functional and morphological characteristics, and endothelium-dependent and -independent dilatory responses were studied in isolated perfused small intrarenal and mesenteric arteries obtained from control rats (CON), rats on LS, lisinopril-treated rats (CON-LIS), or rats treated with lisinopril during LS (LS-LIS). We found, first, that LS-LIS compared with CON-LIS enhances blood pressure reduction. Second, interlobar renal arteries had increased lumen diameter and reduced adrenergic contractility in CON-LIS compared with CON, without additional effects of LS. In contrast, mesenteric arteries were not altered in CON-LIS compared with CON, but became triggered for increased myogenic and adrenergic constriction in LS-LIS. Third, LS-LIS decreased acetylcholine (ACh)-induced vasodilation in both mesenteric and renal arteries compared with CON-LIS. During the latter condition, opposite prostaglandins are involved in the endothelial function of the two different vascular beds, i.e., increased involvement of contractile prostaglandins in ACh-induced vasodilatation in renal arteries, versus dilatory prostaglandins in mesenteric arteries. Whether cause or consequence of the enhanced blood pressure response, our data demonstrate a modifying effect of dietary sodium on vascular effects of ACE inhibition. These findings provide a rationale for further studies addressing the mechanism-of-actions of our therapies to find additional strategies to improve therapy response.Intervention in the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE) inhibitors has proven to be an effective strategy to improve renal and cardiovascular prognosis in different patient populations. The response to ACE inhibition is modified by sodium intake, with a blunted response during high sodium intake, and an enhanced response during dietary sodium restriction. This occurs irrespective of the underlying disorder and applies to the effect on blood pressure, renal hemodynamic response, and proteinuria (Heeg et al., 1989;Teravainen et al., 1997;Buter et al., 1998), in experimental conditions and as well as in humans (Navis et al., 1987;Wapstra et al., 1996;Wing et al., 1998).Although ACE inhibitors have been studied extensively, the mechanism of the modifying effect of sodium intake on their efficacy is not well understood. The effects of ACE inhibition are believed to result from their hemodynamic actions, as well as from pressure-dependent and -independent effect on the vessel wall. In this respect, many studies showed improved vessel wall structure and dimension, and improved endothelial function in cardiovascular disease afte...

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Role of prostanoids in regulation of the renin-angiotensin-aldosterone system by salt intake

Cited by 43 publications

References 40 publications

Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice

Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice

COX-2 activity determines the level of renin expression but is dispensable for acute upregulation of renin expression in rat kidneys

Low Sodium Modifies the Vascular Effects of Angiotensin-Converting Enzyme Inhibitor Therapy in Healthy Rats

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