deoxycholic-acid and Hypertension

Topics: Aldosterone; Angiotensin II; Blood Pressure; Contraceptives, Oral; Deoxycholic Acid; Female; Humans; Hydrocortisone; Hypertension; Renin; Time Factors

Previous findings on hepatic bile acid compositions in nonalcoholic fatty liver disease (NAFLD) have been inconsistent and complicated. The aim of this study was to investigate the effects of steatosis on hepatic bile acid composition in a hypertensive NAFLD model without obesity and diabetes mellitus and compare hepatic bile acid composition between hypertensive rats with and without steatosis.. Two groups of hypertensive rats were studied: spontaneously hypertensive rats (SHR) fed with a normal diet (SHR-N) or a choline-deficient diet (SHR-CD). Two groups of normotensive rats were studied: Wistar Kyoto rats (WKY) fed a normal diet (WKY-N) or a choline-deficient diet (WKY-CD). Hepatic bile acid analysis was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry.. Regarding bile acid composition, the hyodeoxycholic acid (HDCA) species in the SHR-CD group showed the largest change in bile acid composition, significantly decreasing to 21.9% of that found in the SHR-N group. In the WKY-CD group, no reduction of HDCA species was observed.. We demonstrated that the decrease in HDCA species was the main alteration in a hypertensive NAFLD model. It was suggested that the decrease in HDCA species in the SHR-CD group was caused by dysbiosis.

Topics: Animals; Bile Acids and Salts; Choline Deficiency; Chromatography, Liquid; Deoxycholic Acid; Disease Models, Animal; Hypertension; Liver; Male; Non-alcoholic Fatty Liver Disease; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8

Topics: Adoptive Transfer; Animals; CD8-Positive T-Lymphocytes; Chloride Channels; Chlorides; Coculture Techniques; Deoxycholic Acid; Epithelial Cells; Gene Expression Regulation; Hypertension; Ion Transport; Kidney Tubules, Distal; Male; Mice; Mice, Inbred C57BL; Potassium Channels, Inwardly Rectifying; Rats; Reactive Oxygen Species; Signal Transduction; Sodium; Solute Carrier Family 12, Member 3; src-Family Kinases

The mechanisms involved in the cardioprotector effect of red wine have not yet been completely elucidated but probably an endothelium-dependent vasodilator action may play a significant role in this effect. Experiments were undertaken to determine whether a Brazilian red wine (BRW) induces vasodilation in the mesenteric vascular bed (MVB) and an antihypertensive effect was also assessed in rats with NO-deficient hypertension. In MVB precontracted with norepinephrine, BRW (alcohol-free lyophilized) induces a long-lasting endothelium-dependent vasodilation that is not reduced by indomethacin. Inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME) and guanylyl cyclase by 1H-[1,2,3] oxadiazolo [4,4-a]quinoxalin-1-one (ODQ) reduces the vasodilator effect of BRW. In vessels precontracted with norepinephrine and depolarized with KCl (25 Mm) or treated with Ca-dependent K channel blockers charybdotoxin (ChTx) plus apamin, the effect of BRW was significantly reduced. However, this effect is not affected by ATP-dependent K (KATP) channel blocker (glibenclamide). The residual vasodilator effect of BRW observed in vessels pretreated with ChTx plus apamin is completely abolished by ChTx plus apamin plus L-NAME. Concentrations of atropine, pyrilamine, yohimbine, and HOE 140 that significantly reduced the vasodilator effect of acetylcholine, histamine, clonidine, and bradykinin, respectively did not change the vasodilator effect of BRW. Chronic oral administration of BRW induced a significant reduction in systolic, mean and diastolic arterial pressure in rats with L-NAME hypertension. The present results demonstrated that vasodilator effect of BRW is dependent on endothelium-derived hyperpolarizing factor (EDHF) in combination with nitric oxide (NO). The antihypertensive effect of red wine demonstrated in the present study may play a significant role on the cardioprotective action of chronic red wine consumption.

Topics: Acetylcholine; Administration, Oral; Alcohol Drinking; Animals; Apamin; Atropine; Blood Pressure; Bradykinin; Brazil; Charybdotoxin; Clonidine; Deoxycholic Acid; Drug Therapy, Combination; Endothelium, Vascular; Flavonoids; Glyburide; Guanylate Cyclase; Hypertension; Indomethacin; Male; Mesenteric Arteries; Muscle, Smooth, Vascular; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitroglycerin; Norepinephrine; Oxadiazoles; Perfusion; Phenols; Polyphenols; Potassium Chloride; Pressure; Pyrilamine; Quinazolines; Quinoxalines; Rats; Rats, Wistar; Vasoconstriction; Vasodilation; Wine; Yohimbine

Effects of the synthetic bile acids on blood pressure were examined in spontaneously hypertensive rats. Continuous intravenous administration of the bile acids at the rate of 1 mg/min for 20 min significantly lowered the blood pressure by 12 mmHg. In order to examine its blood pressure lowering mechanism, the isolated mesenteric arterial perfusion system was employed. Bile acids in the perfusate inhibited vascular reactivity to norepinephrine and KCl in a dose-dependent manner. This inhibitory action diminished as the concentration of potassium in the perfusate decreased. When the perfusate was free from potassium, its inhibitory action completely disappeared. These results in vivo and in vitro studies strongly suggest that bile acids act directly on the vascular beds and attenuate vascular response to norepinephrine.

Topics: Animals; Bile Acids and Salts; Blood Pressure; Blood Vessels; Deoxycholic Acid; Glycodeoxycholic Acid; Hypertension; Male; Mesenteric Arteries; Norepinephrine; Potassium Chloride; Rats; Rats, Inbred SHR; Rats, Inbred WKY

In female rats aged 21 and 80 days, uninephroadrenalectomy with enucleation of the remaining adrenal was performed and 0.17 mol X l-1 saline offered as the only drinking fluid. The changes of plasma concentration of renin (PRC), and its substrate (RSC) and renal renin activity (RRA), considered as an indicator of the secretory activity of the regenerating adrenal were studied 5, 10, 20, 40 and 60 days after the adrenal enucleation to look for possible age differences related to the higher susceptibility of immature rats to the hypertensive influence of the regenerating adrenal. It has been found that: 1. In adrenal-enucleated rats the saline-induced decrease of RRA was delayed for a shorter time period in immature rats than in adult ones (5 vs. 10 days), during which blood pressure, saline consumption and RSC were lowered. The decrease of PRC was retarded in the older group only. 2. In rats with regenerating adrenals the PRC and RRA decrease was greater in animals subjected to enucleation of the remaining adrenal gland when immature, than in those operated when adult. At the end of the experiment this age difference disappeared. 3. The age difference in PRC and RRA suppression appeared during the period, when neither blood pressure nor saline consumption were higher in immature rats than in adult ones. 4. In rats with regenerating adrenals the renal mass was greater than in saline drinking controls. In the younger group, which in contrast to the adult one developed hypertension, this increase was greater and directly related to the blood pressure level from the 20th post-enucleation day onwards. It is being suggested that the changes of PRC, RRA and RSC observed up to the 10th post-enucleation day indicates relative adrenal insufficiency, the shorter duration of which in immature rats reflects their higher sensitivity to mineralocorticoids produced by the regenerating adrenal. This also manifests itself by greater PRC and RRA suppression in this age group. The haemodynamic results of the greater RRA suppression in the not yet fully developed kidneys of immature rats may facilitate the development of a "vicious circle" mechanism between blood pressure and hypertensive renal damage and thus contribute to the higher sensitivity to adrenal-regeneration hypertension.

Topics: Adrenal Cortex; Adrenalectomy; Age Factors; Animals; Blood Pressure; Deoxycholic Acid; Desoxycorticosterone; Drinking; Female; Hypertension; Kidney; Nephrectomy; Rats; Rats, Inbred Strains; Regeneration; Renin; Renin-Angiotensin System; Sodium Chloride

Studies of ATP hydrolysis by various subcellular fractions isolated from rat mesenteric arteries and veins indicate that an apparent ATPase activity, which can be activated by Mg2+ or Ca2+, is primarily associated with the plasma membranes. Although both Mg2+-activated and Ca2+-activated ATPase activities under the optimal condition are substantially lower in venous than in arterial plasma membrane fraction, their dependence on the concentration of Mg2+ and Ca2+ are quite similar in arterial as well as venous plasma membrane fractions. No synergistic effect on ATP hydrolysis was observed in the presence of both Mg2+ and Ca2+. In addition, Mg2+-activated and Ca2+-activated ATPase activities show similar pH dependence, inhibition by deoxycholate, stability toward heat inactivation and substrate specificity. Furthermore, Mg2+-activated and Ca2+-activated ATPase activities were similarly reduced in vascular smooth muscles of spontaneously hypertensive rats. These results suggest that the activation of ATP hydrolysis by Mg2+ or Ca2+ may represent a single enzyme moiety in the plasma membrane of vascular smooth muscle. The possible involvement of such ATPase in the Ca2+ transport function of vascular smooth muscle is discussed.

Topics: Adenosine Triphosphatases; Animals; Ca(2+) Mg(2+)-ATPase; Calcium-Transporting ATPases; Cell Membrane; Deoxycholic Acid; Female; Hypertension; In Vitro Techniques; Male; Metals; Muscle, Smooth, Vascular; Proteins; Rats; Rats, Inbred Strains; Subcellular Fractions; Vanadates; Vanadium

Bile flow and biliary bile acids were analyzed in arteriolipidosis-prone rats (ALR), the hypertensive model for lipidemic arterial lesions with reactive hypercholesterolemia and compared to those in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Bile flow and bile acid secretion decreased in the order of WKY, SHR and ALR. When labelled cholesterol was given intraperitoneally, the biliary radioactivity secretion was significantly slow in ALR in comparison with that in WKY. The decay of radioactive cholesterol in serum after the injection was also delayed in ALR. Our data suggest that the abnormality in bile flow, biliary bile acid secretion and/or cholesterol turnover to bile acids may be pathogenically related to reactive hypercholesterolemia noted in the ALR.

Topics: Animals; Arteriosclerosis; Bile Acids and Salts; Body Weight; Cholesterol; Cholic Acids; Deoxycholic Acid; Hypertension; Lipidoses; Liver; Male; Rats; Rats, Inbred Strains; Triglycerides