Effect of celecoxib on the antihypertensive effect of losartan in a rat model of renovascular hypertension

2011 ◽  
Vol 89 (2) ◽  
pp. 103-107 ◽  
Author(s):  
Vivian Boshra ◽  
Gehan Abdel Hamid El Wakeel ◽  
Manar A Nader
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Aortic Coarctation ◽  
Oral Treatment ◽  
Antihypertensive Agents ◽  
Plasma Renin ◽  
Prostaglandin E ◽  
Sprague Dawley ◽  
Hypertensive Patients ◽  
Arterial Blood

Certain nonsteroidal anti-inflammatory drugs have been reported to elevate blood pressure in some hypertensive patients, who are either untreated or treated with antihypertensive agents. This study was undertaken to determine the effect of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on the antihypertensive effects of the angiotensin II type 1 receptor (AT1) antagonist, losartan potassium. We studied the effect of oral treatment with losartan (30 mg/kg), celecoxib (3 mg/kg), and their combination on the mean arterial blood pressure (MAP), plasma renin activity (PRA), and plasma prostaglandin E2(PGE2) in male Sprague–Dawley rats with renovascular hypertension (RVH) induced by partial subdiaphragmatic aortic constriction. Treatment was continued for 7 days after aortic coarctation. Aortic coarctation led to significant increases in the MAP, PRA, and plasma PGE2. In RVH rats, losartan treatment caused a significant decrease of MAP with a significant increase in both plasma PGE2and PRA. Celecoxib caused a nonsignificant change in MAP with a significant decrease in the raised levels of plasma PGE2and PRA. Concomitant administration of celecoxib and losartan did not significantly affect the lowering effect of losartan on MAP with a subsequent significant decrease in the plasma PGE2and PRA in RVH rats. Therefore, celecoxib could be used in renin-dependent hypertensive patients who receive losartan, without fear of a rise in their blood pressure.

Role of Prostaglandin in the Antihypertensive Mechanism of Captopril in Low Renin Hypertension

1980 ◽  
Vol 59 (s6) ◽  
pp. 141s-144s ◽  
Author(s):  
Keishi Abe ◽  
Toru Ito ◽  
Makito Sato ◽  
Toshiaki Haruyama ◽  
KO Sato ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Renin Activity ◽  
Prostaglandin E ◽  
Hypertensive Patients ◽  
Endogenous Prostaglandin ◽  
Low Renin Hypertension ◽  
Prostaglandin System

1. The role of endogenous prostaglandins in the antihypertensive mechanism of the angiotensin converting enzyme inhibitor, captopril, was investigated. 2. An unequivocal reduction in blood pressure and significant increase in plasma renin activity and urinary prostaglandin E excretion were found after the captopril administration. 3. The changes in blood pressure, plasma renin activity and urinary prostaglandin E excretion induced by captopril were reversed after the inhibition of endogenous prostaglandin synthesis by indomethacin. However, the responses in low renin hypertension were different from those in normal renin hypertension. 4. In low renin hypertensive patients who responded to captopril, the hypotensive effect was abolished after the addition of indomethacin, whereas no marked change in blood pressure was induced by indomethacin in normal renin hypertensive patients. In contrast, plasma renin activity was markedly increased after captopril administration in normal renin hypertension, and no significant change was found in low renin hypertension. 5. Potentiation of the prostaglandin system seems to be a principal factor in the antihypertensive mechanism of captopril in low renin hypertension, and inhibition of the renin-angiotensin system is important in normal renin hypertensives. 6. The increase in renin release after the administration of captopril was inhibited by indomethacin, suggesting that an endogenous prostaglandin system may contribute to the short feedback mechanism of renin release.

scholarly journals Natriuretic peptides buffer renin-dependent hypertension

2014 ◽  
Vol 306 (12) ◽  
pp. F1489-F1498 ◽  
Author(s):  
Theo Demerath ◽  
Janina Staffel ◽  
Andrea Schreiber ◽  
Daniela Valletta ◽  
Frank Schweda
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Plasma Renin ◽  
Control Mechanisms ◽  
Wild Type ◽  
Renal Vasoconstriction ◽  
Arterial Blood ◽  
Independent Effects

The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP−/−) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP−/− mice were hypertensive and had reduced PRC compared with that in wild-type ANP+/+ mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP−/− mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A−/− mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A+/+ mice. However, the higher blood pressure in GC-A−/− mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A−/− mice than in GC-A+/+ mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II.

VASOPRESSIN RELEASE DURING VENTRICULO-CISTERNAL PERFUSION WITH PROSTAGLANDIN E2 IN THE DOG

1976 ◽  
Vol 71 (3) ◽  
pp. 325-331 ◽  
Author(s):  
MANABU YAMAMOTO ◽  
L. SHARE ◽  
R. E. SHADE
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Plasma Concentrations ◽  
Plasma Osmolality ◽  
Plasma Renin ◽  
Prostaglandin E ◽  
Temperature Plasma ◽  
Vasopressin Release ◽  
Control Value ◽  
Arterial Blood

SUMMARY In an attempt to determine whether prostaglandin E2 (PGE2) can act centrally to affect the release of vasopressin (ADH), the ventriculo-cisternal system of anaesthetized dogs was perfused with PGE2. When PGE2 was perfused at a rate of 76·4 ng/min (0·19 ml/min), the plasma ADH concentration was unchanged. However, perfusion of PGE2 at a rate of 152·8 ng/min (0·19 ml/min) resulted in a significant increase in the plasma ADH concentration from the control value of 9·0 ± 2·2 (s.e.m.) to 18·8 ± 3·9 μu./ml at 10 min and to 41·0 ± 16·7 μu./ml at 30 min after the start of the perfusion. There were no changes in arterial blood pressure, rectal temperature, plasma osmolality, and the plasma concentrations of sodium and potassium. In additional experiments, i.v. injection of indomethacin (2 or 20 mg/kg) decreased the plasma ADH concentration by approximately 50%. Although this finding is consistent with a role of PGE2 in the control of ADH release, it could also have been due to the observed increases in arterial blood pressure and effective left atrial pressure. Plasma renin activity was unchanged in the indomethacin experiments. It is concluded that PGE2 can act in the central nervous system to stimulate ADH release.

Abstract P100: (Pro)renin Receptor (PRR) Mediates Renal Inflammation in Renovascular Hypertension

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Syed Siraj Ahmed Quadri ◽  
Caixia Li ◽  
Silas Culver ◽  
Helmy M Siragy
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Blood Pressure Reduction ◽  
Left Renal Artery ◽  
Sprague Dawley ◽  
Renal Inflammation ◽  
Arterial Blood ◽  
Tnf Α ◽  
Protein Expressions ◽  
Cox 2

We hypothesized that PRR plays a role in renal inflammation in 2-kidney, 1-clip (2K1C) hypertension rat model. Male Sprague-Dawley rats were fed normal sodium diet. BP was obtained before and 28 days after left renal artery clipping. Renal expressions of PRR, TNF-α and COX-2 were assessed in sham and 2K1C rats with or without left renal interstitial administration of scramble shRNA or PRR shRNA. At baseline there were no significant differences in BP between different animal groups. Compared to sham, mean arterial blood pressure significantly increased in 2K1C (2K1C 131.8 ± 3.09 mmHg, vs. sham 108 ± 1.9 mmHg, P<0.0.05) at day 28 and was not influenced by scramble shRNA or PRR shRNA treatment. Compared to sham and contra lateral (non-clipped) kidney, there were increases in mRNA and protein expressions of PRR (90% and 45%, P<0.01), TNF-α (72% and 50%, P<0.05), COX-2 (72% and 39%, P<0.05) in the clipped kidney. These expressions were not influenced by scramble shRNA treatment. Compared to 2K1C (no treatment) and scramble shRNA, PRR shRNA treatment in the clipped kidney caused significant reductions in mRNA and protein expressions of PRR (60% and 54%, P<0.01, shown in figure below), TNF-α (54% and 51%, P<0.05), COX-2 (51% and 53%, P<0.05). We conclude that PRR mediates renal inflammation in renovascular hypertension independent of blood pressure reduction.

scholarly journals Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension

2008 ◽  
Vol 295 (5) ◽  
pp. R1546-R1554 ◽  
Author(s):  
Melissa Li ◽  
Xiaoling Dai ◽  
Stephanie Watts ◽  
David Kreulen ◽  
Gregory Fink
Keyword(s):  
Blood Pressure ◽  
Sympathetic Innervation ◽  
Sympathetic Ganglia ◽  
Plasma Norepinephrine ◽  
Sprague Dawley ◽  
Surgical Ablation ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Hypertension Development

Endothelin (ET) type B receptors (ETBR) are expressed in multiple tissues and perform different functions depending on their location. ETBR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ETBR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia.

scholarly journals Accumulation of Prostacyclin in Rat Brain during Haemorrhagic Hypotension—Possible Role of PGI2 in Autoregulation

1984 ◽  
Vol 4 (1) ◽  
pp. 107-109 ◽  
Author(s):  
E. Shohami ◽  
A. Sidi
Keyword(s):  
Blood Pressure ◽  
Steady State ◽  
Control Group ◽  
Prostaglandin E ◽  
Cortical Tissue ◽  
Arterial Blood ◽  
Haemorrhagic Hypotension ◽  
Potent Vasodilator ◽  
Prostaglandin F

The effect of haemorrhagic hypotension on the levels of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto prostaglandin F1α (6-keto-PGF1α) in cortical tissue of rats was studied. Lightly anesthetized rats were subjected to steady-state hypotension for 15 min, with a mean arterial blood pressure of 80, 60, and 40 mm Hg, and compared to a control group of normotensive rats. No significant change was found in the levels of PGE2 and TXB2. The level of 6-keto-PGF1α increased from 7.8 ± 0.9 to 14.1 ± 1.9 pg/mg protein (p < 0.02) at 80 mm Hg. Our findings suggest that prostacyclin, which is a potent vasodilator, might play a role in setting the lower limit of the autoregulation range.

Enhancement of the Antihypertensive Effect of Hydrochlorothiazide in Dogs after Suppression of Renin Release by Beta-Adrenergic Blockade

1975 ◽  
Vol 48 (2) ◽  
pp. 147-151
Author(s):  
C. S. Sweet ◽  
M. Mandradjieff
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Arterial Blood Pressure ◽  
Antihypertensive Effect ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
Antihypertensive Activity ◽  
Adrenergic Blockade ◽  
Arterial Blood

1. Renal hypertensive dogs were treated with hydrochlorothiazide (8−2 μmol/kg or 33 μmol/kg daily for 7 days), or timolol (4.6 μmol/kg daily for 4 days), a potent β-adrenergic blocking agent, or combinations of these drugs). Changes in mean arterial blood pressure and plasma renin activity were measured over the treatment period. 2. Neither drug significantly lowered arterial blood pressure when administered alone. Plasma renin activity, which did not change during treatment with timolol, was substantially elevated during treatment with hydrochlorothiazide. 3. When timolol was administered concomitantly with hydrochlorothiazide, plasma renin activity was suppressed and blood pressure was significantly lowered. 4. These observations suggest that compensatory activation of the renin-angiotensin system limits the antihypertensive activity of hydrochlorothiazide in renal hypertensive dogs and suppression of diuretic-induced renin release by timolol unmasks the antihypertensive effect of the diuretic.

scholarly journals Salt sensitivity of blood pressure in NKCC1-deficient mice

2008 ◽  
Vol 295 (4) ◽  
pp. F1230-F1238 ◽  
Author(s):  
Soo Mi Kim ◽  
Christoph Eisner ◽  
Robert Faulhaber-Walter ◽  
Diane Mizel ◽  
Susan M. Wall ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Wheel Running ◽  
Plasma Renin ◽  
Pressure Change ◽  
Standard Diet ◽  
Wild Type ◽  
Vascular Effects ◽  
Arterial Blood ◽  
Deficient Mice

NKCC1 is a widely expressed isoform of the Na-2Cl-K cotransporter that mediates several direct and indirect vascular effects and regulates expression and release of renin. In this study, we used NKCC1-deficient (NKCC1−/−) and wild-type (WT) mice to assess day/night differences of blood pressure (BP), locomotor activity, and renin release and to study the effects of high (8%) or low (0.03%) dietary NaCl intake on BP, activity, and the renin/aldosterone system. On a standard diet, 24-h mean arterial blood pressure (MAP) and heart rate determined by radiotelemetry, and their day/night differences, were not different in NKCC1−/− and WT mice. Spontaneous and wheel-running activities in the active night phase were lower in NKCC1−/− than WT mice. In NKCC1−/− mice on a high-NaCl diet, MAP increased by 10 mmHg in the night without changes in heart rate. In contrast, there was no salt-dependent blood pressure change in WT mice. MAP reductions by hydralazine (1 mg/kg) or isoproterenol (10 μg/mouse) were significantly greater in NKCC1−/− than WT mice. Plasma renin (PRC; ng ANG I·ml−1·h−1) and aldosterone (aldo; pg/ml) concentrations were higher in NKCC1−/− than WT mice (PRC: 3,745 ± 377 vs. 1,245 ± 364; aldo: 763 ± 136 vs. 327 ± 98). Hyperreninism and hyperaldosteronism were found in NKCC1−/− mice during both day and night. High Na suppressed PRC and aldosterone in both NKCC1−/− and WT mice, whereas a low-Na diet increased PRC and aldosterone in WT but not NKCC1−/− mice. We conclude that 24-h MAP and MAP circadian rhythms do not differ between NKCC1−/− and WT mice on a standard diet, probably reflecting a balance between anti- and prohypertensive factors, but that blood pressure of NKCC1−/− mice is more sensitive to increases and decreases of Na intake.

Effect of linoleic acid infusion on blood pressure in normotensive and hypertensive rats

1989 ◽  
Vol 257 (2) ◽  
pp. H611-H617 ◽  
Author(s):  
S. R. Reddy ◽  
R. Talwalkar ◽  
J. Downs ◽  
T. A. Kotchen
Keyword(s):  
Blood Pressure ◽  
Linoleic Acid ◽  
Sodium Chloride ◽  
Enzymatic Activity ◽  
Plasma Renin ◽  
Sprague Dawley ◽  
Acid Infusion ◽  
High Sodium ◽  
Hypotensive Response

High dietary intake of linoleic acid lowers arterial pressure, and, in vitro, linoleic acid inhibits the enzymatic activity of renin. The purpose of the present study was 1) to evaluate the effect of intravenous infusion of linoleic acid on blood pressure in normotensive and hypertensive Sprague-Dawley rats and 2) to determine whether the hypotensive response to linoleic acid infusion is caused by inhibition of circulating renin. Blood pressure was decreased (P less than 0.01) by linoleic acid infusion in normotensive sodium chloride-deprived animals and in animals with two-kidney, one-clip hypertension. In contrast, linoleic acid infusion did not affect blood pressure in normotensive rats on a "normal" or high sodium chloride intake, in rats with deoxycorticosterone acetate (DOCA)-salt hypertension, and in anephric rats. In sodium chloride-deprived rats, the reduction of blood pressure by linoleic acid infusion was associated with increased plasma renin activity (P less than 0.05); serum angiotensin-converting enzyme activity was unchanged. The in vitro enzymatic activity of exogenous renin in plasma of anephric rats was not affected by linoleic acid infusion. In two-kidney, one-clip hypertensive animals, pretreatment with indomethacin did not alter the hypotensive response to linoleic acid. Thus, although linoleic acid infusion lowered blood pressure in high renin but not in low renin states, the reduction of blood pressure was not related to inhibition of circulating renin or to alterations of endogenous prostaglandin biosynthesis.

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