Mean Arterial Pressure In Normotensive Rats Research Articles

The effect of celecoxib on blood pressure and plasma oxidant/antioxidant status in co-administration with glucocorticoid in rat.

There is limited information about the concomitant uses of selective COX-2 inhibitors with corticosteroids or with antihypertensive medications. The aim of this study was to investigate the effect of celecoxib on blood pressure and plasma oxidant/antioxidant status in glucocorticoid-induced hypertension and in co-administration with captopril. Male Wistar rats received dexamethasone (30 μg/kg/day, s.c.) for 14 days. The tested groups received dexamethasone and orally treated with celecoxib (10, 25 or 50 mg/kg) or captopril (10, 20 or 40 mg/kg) or celecoxib (50 mg/kg) + captopril from day 8 to 14. Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were measured using tail-cuff method. Hydroperoxides concentration and ferric reducing antioxidant power (FRAP) value were determined in plasma samples. Dexamethasone significantly increased BP and plasma hydroperoxides level and decreased body weights. High dose of celecoxib resulted in a small but significant increase in SBP, DBP and MAP in normotensive rats however it did not alter BP markers in dexamethasone-induced hypertensive rats. Celecoxib reduced the hypotensive effect of all doses of captopril in dexamethasone-induced hypertensive rats however the SBP and MAP was preserved near to normal at low and middle doses of captopril but DBP was more than normal at low dose of captopril. Heart rate was not significantly altered by different treatments. High dose of celecoxib also increased plasma hydroperoxides concentration without effect on FRAP level. In conclusion, celecoxib did not change blood pressure in glucocorticoid-induced hypertensive rats but may blunt the hypotensive effect of low dose of captopril. Further studies are needed for detailed information addressing the effects of COX-2 inhibitors on blood pressure in concomitant uses with corticosteroids.

Heme Oxygenase-1 Overexpression Fails to Attenuate Hypertension when the Nitric Oxide Synthase System Is Not Fully Operative

Heme oxygenase (HO) is an enzyme that is involved in numerous secondary actions. One of its products, CO, seems to have an important but unclear role in blood pressure regulation. CO exhibits a vasodilator action through the activation of soluble guanylate cyclase and the subsequent production of cyclic guanosine monophosphate (cGMP). The aim of the present study was to determine whether pathological and pharmacological HO-1 overexpression has any regulatory role on blood pressure in a renovascular model of hypertension. We examined the effect of zinc protoporyphyrin IX (ZnPP-IX) administration, an inhibitor of HO activity, on mean arterial pressure (MAP) and heart rate in sham-operated and aorta-coarcted (AC) rats and its interaction with the nitric oxide synthase (NOS) pathway. Inhibition of HO increased MAP in normotensive rats with and without hemin pretreatment but not in hypertensive rats. Pretreatment with NG-nitro-L-arginine methyl ester blocked the pressor response to ZnPP-IX, suggesting a key role of NOS in the cardiovascular action of HO inhibition. In the same way, AC rats, an experimental model of hypertension with impaired function and low expression of endothelial NOS (eNOS), did not show any cardiovascular response to inhibition or induction of HO. This finding suggests that eNOS was necessary for modulating the CO response in the hypertensive group. In conclusion, the present study suggests that HO regulates blood pressure through CO only when the NOS pathway is fully operative. In addition, chronic HO induction fails to attenuate the hypertensive stage induced by coarctation as a consequence of the impairment of the NOS pathway.

Dalcetrapib: no off‐target toxicity on blood pressure or on genes related to the renin‐angiotensin‐aldosterone system in rats

The association between torcetrapib and its off-target effects on blood pressure suggested a possible class-specific effect. The effects of dalcetrapib (RO4607381/JTT-705) and torcetrapib on haemodynamics and the renin-angiotensin-aldosterone system (RAAS) were therefore assessed in a rat model. Arterial pressure (AP) and heart rate were measured by telemetry in normotensive and spontaneously hypertensive rats (SHR) receiving torcetrapib 10, 40 or 80 mg kg(-1) day(-1); dalcetrapib 100, 300 or 500 mg(-1) kg day(-1); or vehicle (placebo) for 5 days. Expression of RAAS genes in adrenal gland, kidney, aorta and lung from normotensive rats following 5 days' treatment with torcetrapib 40 mg kg(-1) day(-1), dalcetrapib 500 mg kg(-1) day(-1) or vehicle was measured by quantitative polymerase chain reaction. Torcetrapib transiently increased mean AP in normotensive rats (+3.7 +/- 0.1 mmHg), whereas treatment in SHR resulted in a dose-dependent and sustained increase [+6.5 +/- 0.6 mmHg with 40 mg kg(-1) day(-1) at day 1 (P < 0.05 versus placebo)], which lasted over the treatment period. No changes in AP or heart rate were observed with dalcetrapib. Torcetrapib, but not dalcetrapib, increased RAAS-related mRNAs in adrenal glands and aortas. In contrast to torcetrapib, dalcetrapib did not increase blood pressure or RAAS-related gene expression in rats, suggesting that the off-target effects of torcetrapib are not a common feature of all compounds acting on cholesteryl ester transfer protein.

Studies on antihypertensive and antispasmodic activities of Andropogon muricatus Retz.This article is one of a selection of papers published in this special issue (part 1 of 2) on the Safety and Efficacy of Natural Health Products.

The aqueous-methanolic crude extract of Andropogon muricatus (Am.Cr) was investigated pharmacologically to determine some of its medicinal uses in cardiovascular and gastrointestinal disorders. A series of in vivo and in vitro studies were conducted to evaluate dose-dependent effects of Am.Cr on mean arterial pressure (MAP), cardiac and vascular contractions, and to further investigate the potential mechanism of action. Intravenous administration of Am.Cr (10-50 mg/kg) caused a fall (18%-56%) in MAP in normotensive rats under anesthesia. When tested in isolated guinea pig atria, Am.Cr (0.03-5.0 mg/mL) exhibited a cardiodepressant effect on the rate and force of spontaneous contractions. In isolated rabbit aorta, Am.Cr caused inhibition of K+ (80 mmol/L)-induced contractions at a lower concentration than of phenylephrine. In isolated rabbit jejunum preparations, Am.Cr (0.01-0.10 mg/mL) caused relaxation of spontaneous and high K+ (80 mmol/L)-induced contractions, suggesting that the spasmolytic effect is mediated possibly through calcium channel blockade (CCB). The CCB activity was confirmed when pretreatment of the tissue with Am.Cr (0.03-0.1 mg/mL) shifted the Ca2+ dose-response curves to the right, similar to that caused by verapamil. These data indicate that the blood pressure-lowering and spasmolytic effects of Am.Cr are mediated possibly through a calcium channel blocking activity. Phytochemical screening of Am.Cr revealed the presence of phenols, saponins, tannins, and terpenes, which may be responsible for the observed vasodilator, cardiodepressant, and antispasmodic activities. This study shows potential with respect to its medicinal use in cardiovascular and gut disorders.

Cyclooxygenase-2 inhibition normalizes arterial blood pressure in CYP1A1-REN2 transgenic rats with inducible ANG II-dependent malignant hypertension

The present study was performed to determine the effects of cyclooxygenase (COX)-1 and COX-2 inhibition on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Male Cyp1a1-Ren2 rats (n = 7) were fed a normal diet containing the aryl hydrocarbon, indole-3-carbinol (I3C; 0.3%), for 6-9 days to induce malignant hypertension. Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats during control conditions, following administration of the COX-2 inhibitor nimesulide (3 mg/kg iv), and following administration of the nonspecific COX inhibitor meclofenamate (5 mg/kg iv). Rats induced with I3C had higher MAP than noninduced rats (n = 7; 188 +/- 6 vs. 136 +/- 4 mmHg, P < 0.01). There was no difference in renal plasma flow (RPF) or glomerular filtration rate (GFR) between induced and noninduced rats. Nimesulide elicited a larger decrease in MAP in hypertensive rats (188 +/- 6 to 140 +/- 8 mmHg, P < 0.01) than in normotensive rats (136 +/- 4 to 113 +/- 8 mmHg, P < 0.01). Additionally, nimesulide decreased GFR (0.9 +/- 0.13 to 0.44 +/- 0.05 ml.min(-1).g(-1), P < 0.05) and RPF (2.79 +/- 0.27 to 1.35 +/- 0.14 ml.min(-1).g(-1), P < 0.05) in hypertensive rats but did not alter GFR or RPF in normotensive rats. Meclofenamate further decreased MAP in hypertensive rats (to 115 +/- 10 mmHg, P < 0.05) but did not decrease MAP in normotensive rats. Meclofenamate did not alter GFR or RPF in either group. These findings demonstrate that COX-1- and COX-2-derived prostanoids contribute importantly to the development of malignant hypertension in Cyp1a1-Ren2 transgenic rats. The data also indicate that COX-2-derived vasodilatory metabolites play an important role in the maintenance of RPF and GFR following induction of malignant hypertension in Cyp1a1-Ren2 transgenic rats.

Effects of the ET(A)/ET(B) antagonist, TAK-044, on blood pressure and renal excretory function after unclipping of conscious one-kidney-one-clip hypertensive rats.

Restoring renal perfusion pressure (unclipping) of one-kidney-one-clip renal hypertensive (1 K1C) rats normalizes mean arterial pressure (MAP) rapidly. This has been attributed to salt/volume losses or release of the putative renal medullary depressor hormone (RMDH). To investigate the effects of endothelin receptor A and B (ET(A)/ET(B)) antagonism on unclipping. Telemetric devices were implanted in male Wistar 1K1C rats for measurement of conscious MAP. Hypertension was reversed by unclipping with the animal under brief anaesthesia. Seven rats were treated with the ET(A)/ET(B) antagonist, TAK-044 (two doses of 10 mg/kg intraperitoneally in 24 h), and eight rats received its vehicle. In order to investigate whether endothelin receptor antagonism could release RMDH under resting conditions, TAK-044 was administered to telemetered non-clipped intact and chemically renal medullectomized rats (BEA treatment). TAK-044 did not affect resting MAP, urine flow or sodium excretion in 1K1C rats. However, after unclipping, the TAK-044-treated group showed a more marked reduction in MAP during the first 24 h after unclipping (P< 0.01). TAK-044 also reduced urine flow and sodium excretion during the first 8 h after unclipping (P< 0.05). TAK-044 reduced resting MAP (P< 0.05) to a similar extent in intact and BEA rats. TAK-044 potentiated the reduction in MAP after unclipping, independently of changes in urine flow and sodium excretion. It also reduced MAP in normotensive rats--an effect that was not dependent on an intact renal medulla. Potentiation of the depressor response to unclipping by TAK-044 could be the result of an interaction of endogenous endothelin receptors with renal depressor mechanisms--possibly, the release, actions, or both, of the putative RMDH.