Inhibition of NHE3-mediated Sodium Absorption in the Gut Reduced Cardiac End-organ Damage Without Deteriorating Renal Function in Obese Spontaneously Hypertensive Rats.

Abstract:

:Increased sodium absorption in the gut is one mechanism contributing to hypertensive blood pressure values. The sodium-proton-exchanger subtype 3 (NHE3) is an important mediator of intestinal sodium absorption. The compound SAR is a new specific NHE3 inhibitor with extremely low oral absorbability leading to decreased sodium absorption in the gut and substantial systolic blood pressure reduction. The effects of intestinal NHE3 inhibition on cardiac and renal hypertensive end-organ damage are unknown. The effects of SAR (1 mg·kg⁻¹·d⁻¹ in chow) on left ventricular (LV) and renal remodeling processes were studied by magnetic resonance imaging and biochemical and histological analysis in obese spontaneously hypertensive rats (SHR-ob SAR) compared with placebo-treated SHR-ob (SHR-ob PLAC). Inhibition of intestinal NHE3 by SAR lowered blood pressure and reduced LV end-diastolic pressure from 21 ± 3.0 to 15 ± 2.0 mm Hg (P = 0.0016), whereas heart rate kept unchanged. LV mass indices, LV myocyte diameters, and LV fibrosis formation were lower in SHR-ob SAR compared with SHR-ob PLAC. SAR did not influence urinary albumin to creatinine ratio or glomerular filtration rate. Renal interstitial fibrosis formation, as well as podocyte damage and glomerulosclerosis remained unchanged. Reduction of intestinal sodium absorption by selective NHE3 inhibition in the gut lowered high blood pressure and reduced LV remodeling without deteriorating renal functional and structural parameters in SHR-ob.

journal_name

J Cardiovasc Pharmacol

authors

Linz B,Hohl M,Reil JC,Böhm M,Linz D

doi

10.1097/FJC.0000000000000336

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

225-31

issue

3

eissn

0160-2446

issn

1533-4023

journal_volume

67

pub_type

杂志文章
  • CE inhibition and natriuresis with ramipril in conscious SHR: different modes of action of loop and thiazide diuretics.

    abstract::Acute effects of piretanide, a loop diuretic, on blood pressure (BP) and urinary output as well as long-term effects on serum electrolytes were compared in conscious spontaneously hypertensive rats (SHR) to that of hydrochlorothiazide (HCT) both given alone and in combination with the converting enzyme (CE) inhibitor ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198706107-00030

    authors: Becker RH,Baldes L,Treudler M

    更新日期:1987-01-01 00:00:00

  • Effects of histamine on porcine isolated myocardium: differentiation from effects on human tissue.

    abstract::Inotropic effects of histamine have been studied extensively in many species, but data on porcine myocardium, often used as a model for human heart, are not available. We investigated inotropic effects of histamine on atrial and ventricular trabeculae obtained from porcine hearts. For comparison, we also evaluated the...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199309000-00019

    authors: Du XY,Schoemaker RG,X462P6,Bos E,Saxena PR

    更新日期:1993-09-01 00:00:00

  • Orally administered rapamycin does not modify rat aortic vascular tone.

    abstract::Rapamycin (RP; rapamune, sirolimus) is a potent inhibitor of vascular smooth muscle cell proliferation and migration. RP was demonstrated to reduce vascular neointimal formation in different animal models of vascular smooth muscle cell proliferation, and clinical use of RP-eluting stents promotes significant reduction...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e31802e6420

    authors: Neto Mde M,Di Marco GS,Casarini DE,Lima VC,Campos AH

    更新日期:2007-02-01 00:00:00

  • Differential effects of alpha 1- and alpha 2-adrenoceptor agonists on peripheral vasoconstriction in pithed diabetic rats.

    abstract::The pressor responses to selective alpha 1-adrenoceptor agonists (cirazoline and methoxamine) and to alpha 2-adrenoceptor agonists (UK-14,304 and B-HT 933) were investigated in pithed, streptozotocin-induced diabetic rats and age-matched control animals. Three months after induction of diabetes, the basal values of di...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199210000-00007

    authors: Heijnis JB,Mathy MJ,Pfaffendorf M,van Zwieten PA

    更新日期:1992-10-01 00:00:00

  • Effects of felodipine, a new dihydropyridine vasodilator, on regional myocardial blood flow during acute coronary occlusion in the pig.

    abstract::We studied the effects of felodipine [4-(2,3-dichlorophenyl)-1,4-dihydropyridine-2,6-dimethyl 3,5-dicarboxylic 3-ethylester and 5-methylester] on the coronary vascular bed of pig hearts with an ischemic region in the left ventricle following ligation of the left anterior descending coronary artery. At an infusion rate...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198303000-00006

    authors: Sjöquist PO,Adler G,Duker G,Almgren O

    更新日期:1983-03-01 00:00:00

  • Loss of endothelium-dependent relaxation in proximal pulmonary arteries from rats exposed to chronic hypoxia: effects of in vivo and in vitro supplementation with L-arginine.

    abstract::To explore endothelium-dependent relaxation and the L-arginine (L-ARG)-nitric oxide (NO) pathway during chronic hypoxia, we examined isolated rings from large conduit pulmonary arteries and aorta from rats exposed to either room air (N), 3-week hypoxia (H), or 3-week H followed by 72-h recovery to normoxia (room air)....

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199312000-00018

    authors: Carville C,Raffestin B,Eddahibi S,Blouquit Y,Adnot S

    更新日期:1993-12-01 00:00:00

  • Nicotine enhances angina pectoris-like chest pain and atrioventricular blockade provoked by intravenous bolus of adenosine in healthy volunteers.

    abstract::An attempt was made to study possible interaction between neuromodulation by adenosine and nicotine stimulatory effects. Dose-effect curves were made double blind in 7 nonsmoking, nonsnuffing healthy volunteers (25-49 years) before and during exposition to nicotine roughly corresponding to the nicotine of one cigarett...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199012000-00015

    authors: Sylvén C,Beermann B,Kaijser L,Jonzon B

    更新日期:1990-12-01 00:00:00

  • A comparison of the cellular electrophysiology of mexiletine and sotalol, singly and combined, in canine Purkinje fibers.

    abstract::To determine if combinations of mexiletine and sotalol retain Class I and III electrophysiologic actions, using standard microelectrode techniques, we examined the electrophysiologic effects on canine Purkinje fibers of solutions of mexiletine (3.1-100 microM), sotalol (3.1-400 microM), and combinations of the two dru...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198809000-00005

    authors: Berman ND,Loukides JE

    更新日期:1988-09-01 00:00:00

  • Protective effects of cyclopiazonic acid on ischemia-reperfusion injury in rabbit hearts.

    abstract::The cardioprotective effects on myocardial ischemia of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) inhibitor, cyclopiazonic acid (CPA), were studied. We used the isolated arterially perfused interventricular septum of the rabbit heart submitted to 30-min global ischemia/30-min reperfusion. Mechanical [maximal ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199811000-00022

    authors: Avellanal M,Rodriguez P,Barrigon S

    更新日期:1998-11-01 00:00:00

  • Prostaglandins.

    abstract::A discussion of important aspects of the effects of prostaglandins on arteries must include (a) the nature of the receptors for the different humoral agents, (b) the potential modulatory role that endogenously produced prostaglandins may play when other vasoactive hormones are present, and (c) the potential for cell-t...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198406002-00016

    authors: Aiken JW

    更新日期:1984-01-01 00:00:00

  • Effects of adrenergic antihypertensive drugs on sterol synthesis in freshly isolated human mononuclear leukocytes.

    abstract::The effects of the adrenergic antihypertensive drugs propranolol, clonidine, alpha-methyldopa, urapidil, indoramin, and prazosin on the relative rate of sterol synthesis were studied in freshly isolated human mononuclear leukocytes. Incubation of cells for 6 h in a medium containing lipid-depleted serum led to a three...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198511000-00019

    authors: Krone W,Müller-Wieland D,Greten H

    更新日期:1985-11-01 00:00:00

  • Age-related effects of converting enzyme inhibitors: a commentary.

    abstract::Experience with angiotensin converting enzyme (ACE) inhibitor drugs as with other antihypertensive agents, is limited in the elderly. Nevertheless, they appear effective and well tolerated but without evidence to suggest that they have any special role in the elderly compared to a younger age group. Most are excreted ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:

    authors: Ball SG

    更新日期:1988-01-01 00:00:00

  • Aspirin Use in Secondary Cardiovascular Protection and the Development of Aspirin-Associated Erosions and Ulcers.

    abstract::Aspirin for secondary cardiovascular disease prevention is well established, but treatment discontinuation, often because of gastrointestinal mucosal injury or symptoms, can lead to increased risk for cardiovascular events. Proton pump inhibitor therapy is recommended for aspirin-treated patients at gastrointestinal r...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/FJC.0000000000000387

    authors: Goldstein JL,Scheiman JM,Fort JG,Whellan DJ

    更新日期:2016-08-01 00:00:00

  • Biochemical mechanisms for the inotropic effect of the cardiotonic drug milrinone.

    abstract::Milrinone is a new inotropic agent for the treatment of refractory congestive heart failure. Our understanding of the mechanisms(s) of action of this synthetic cardiotonic drug is incomplete. We examined the effects of milrinone and the parent compound amrinone on sarcoplasmic reticulum function (45Ca-uptake and Ca-AT...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198709010-00031

    authors: Earl CQ,Linden J,Weglicki WB

    更新日期:1986-07-01 00:00:00

  • Resident cardiac mast cells and the cardioprotective effect of ischemic preconditioning in isolated rat heart.

    abstract::Our study was designed to investigate the role of resident cardiac mast cells in the cardioprotective effect of ischemic preconditioning. Ischemic/compound 48/80 preconditioning and treatment with compound 48/80, a mast cell degranulator (1 microg/ml), produced cardioprotective and antiarrhythmic effects in isolated p...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199708000-00001

    authors: Parikh V,Singh M

    更新日期:1997-08-01 00:00:00

  • Clinical pharmacokinetics of intravenous and oral bretylium tosylate in survivors of ventricular tachycardia or fibrillation: clinical application of a new assay for bretylium.

    abstract::We studied 12 patients receiving either chronic oral (p.o.) maintenance bretylium and/or acute intravenous (i.v.) bretylium to evaluate drug efficacy and pharmacokinetics. All patients were survivors of ventricular tachycardia or fibrillation. A new assay for bretylium was applied, and it proved sensitive and reliable...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-198105000-00008

    authors: Anderson JL,Patterson E,Wagner JG,Johnson TA,Lucchesi BR,Pitt B

    更新日期:1981-05-01 00:00:00

  • Effects of angiotensin-(1-7) on the proliferation and collagen synthesis of arginine vasopressin-stimulated rat cardiac fibroblasts: role of mas receptor-calcineurin-NF-κB signaling pathway.

    abstract::: Interstitial fibrosis is a common pathological change in various heart diseases, especially cardiac hypertrophy. Arginine vasopressin (AVP), one of the hallmarks of heart failure, exhibits a profibrotic effect by promoting the proliferation and differentiation of cardiac fibroblasts (CFs). In contrast, angiotensin-(...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0000000000000151

    authors: Niu X,Xue Y,Li X,He Y,Zhao X,Xu M,Zhao L

    更新日期:2014-12-01 00:00:00

  • Endothelin/nitric oxide balance influences hepatic ischemia-reperfusion injury.

    abstract::During ischemia-reperfusion an imbalance between endothelin (ET) and nitric oxide (NO) can be responsible for microcirculatory disturbances. The aim of this study was to restore the ET/NO balance to reduce the ischemia-reperfusion injury. Hepatic ischemia was induced for 30 min in 56 Wistar rats. Sham operation, ische...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200036051-00064

    authors: Uhlmann D,Uhlmann S,Spiegel HU

    更新日期:2000-11-01 00:00:00

  • An Orally Available NLRP3 Inflammasome Inhibitor Prevents Western Diet-Induced Cardiac Dysfunction in Mice.

    abstract:BACKGROUND:A diet rich in saturated fat and sugars (Western diet, WD) induces myocardial expression of the NLRP3 inflammasome and dysfunction in mice. We therefore hypothesized that a diet enriched with an orally available NLRP3 inflammasome inhibitor could prevent WD-induced cardiac dysfunction in mice. METHODS:Ten-w...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0000000000000628

    authors: Carbone S,Mauro AG,Prestamburgo A,Halquist MS,Narayan P,Potere N,Mezzaroma E,Van Tassell BW,Abbate A,Toldo S

    更新日期:2018-12-01 00:00:00

  • Cardiac Na+ channel activation as a positive inotropic principle.

    abstract::This article reviews the relation of cardiac cellular Na+ load and increased force of contraction. Digitalis glycosides and naturally occurring Na+ channel activators are considered. DPI201-106 was described as the first synthetic organic molecule with cardioselective Na+ channel-activating properties and investigated...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/00005344-198914003-00006

    authors: Scholtysik G

    更新日期:1989-01-01 00:00:00

  • Evaluation of the indomethacin-nitroglycerin interaction with positron-emission tomography.

    abstract::The hypothesis that local release of prostanoids may contribute to the pharmacologic effect of nitroglycerin (NTG) has long been debated. Results of prostanoid blockade by indomethacin on NTG-induced effects, to date, have been inconclusive. To quantitate the effects of intravenous indomethacin on NTG-induced myocardi...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00005344-199712000-00005

    authors: Bednarcyzk EM,Furniss SM,Green JA,Munger MA

    更新日期:1997-12-01 00:00:00

  • Acute effects of endothelin-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) in rats with dilated cardiomyopathy.

    abstract::The hemodynamic effects of endothelin (ET)-1 and TAK-044 (ET(A) and ET(B) receptor antagonist) were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Six weeks after immunization, survived Lewis rats (30/43 = 70%) were randomly allocated into five groups to be given 0, 0.3, 3, 30 and 60 mg...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200000006-00011

    authors: Watanabe K,Ohta Y,Kouda T,Sekiguchi T,Sato S,Nakazawa M,Hasegawa G,Naito M,Fuse K,Ito M,Hirono S,Tanabe N,Hanawa H,Kato K,Kodama M,Aizawa Y

    更新日期:2000-01-01 00:00:00

  • Carvedilol is effective and safe in combination with bepridil for persistent atrial fibrillation and decreases the QT prolongation induced by bepridil therapy.

    abstract:INTRODUCTION:We investigated the efficacy of carvedilol for preventing the recurrence of atrial fibrillation and reducing QT prolongation induced by bepridil. METHODS:We assigned 144 subjects with persistent atrial fibrillation. The subjects were divided into 3 groups: carvedilol plus bepridil, candesartan plus beprid...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/FJC.0b013e3182790692

    authors: Kawamura M,Munetsugu Y,Tanno K,Kobayashi Y

    更新日期:2013-01-01 00:00:00

  • Protective effect of PNU-120596, a selective alpha7 nicotinic acetylcholine receptor-positive allosteric modulator, on myocardial ischemia-reperfusion injury in rats.

    abstract::The cholinergic anti-inflammatory pathway has been found to exert a protective role in myocardial ischemia-reperfusion injury (MIRI). Alpha7 nicotinic acetylcholine receptor (α7nAChR) is a regulator of cholinergic anti-inflammatory pathway; however, little information is available on the effect of α7nAChR on MIRI. In ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/FJC.0b013e31824c86c3

    authors: Li H,Zhang ZZ,Zhan J,He XH,Song XM,Wang YL

    更新日期:2012-06-01 00:00:00

  • Antiarrhythmic and electrophysiologic effects of ibutilide in a chronic canine model of atrial flutter.

    abstract::We studied the effects of orally administered ibutilide, a class III antiarrhythmic agent, in a model of reentrant atrial flutter in conscious dogs. After baseline determination of atrial effective refractory period (AERP) and demonstration of reproducible induction of atrial flutter by rapid atrial pacing, 8 dogs rec...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199307000-00002

    authors: Buchanan LV,Turcotte UM,Kabell GG,Gibson JK

    更新日期:1993-07-01 00:00:00

  • Brain-stem mechanisms governing resting and reflex tone of precapillary vessels.

    abstract::The sympathetic drive to the cardiovascular system depends on the integrity of neurons in the medulla oblongata. The adrenergic neurons of the C1-area of the cortical ventrolateral medulla are tonically active and provide the background excitation of the spinal preganglionic neurons, which relay to the postganglionic ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/00005344-198500073-00019

    authors: Reis DJ

    更新日期:1985-01-01 00:00:00

  • Endothelin-2-converting enzyme from human renal adenocarcinoma cells is a phosphoramidon-sensitive, membrane-bound metalloprotease.

    abstract::From the membrane fraction of cultured human renal adenocarcinoma (ACHN) cells, two endothelin-2-converting enzymes (ECE-2A and ECE-2B) were solubilized with detergent Lubrol PX and separated by hydrophobic butyl fast-performance liquid chromatography. The pH range of the converting activity of ECE-2B for big endothel...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199322008-00018

    authors: Shinmi O,Yorimitsu K,Moroi K,Nishiyama M,Sugita Y,Saito T,Inagaki Y,Masaki T,Kimura S

    更新日期:1993-01-01 00:00:00

  • Comparison of vasoconstrictor actions of endothelin-1 in cerebral, coronary, and mesenteric arteries of the dog.

    abstract::Vasoconstrictor actions of endothelin-1 (ET) were compared between endothelium-removed strips of cerebral (basilar, posterior cerebral, and middle cerebral) and peripheral (coronary and mesenteric) arteries of the dog. ET produced a concentration-dependent contraction in these arteries. A threshold concentration and E...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-199204000-00014

    authors: Tanoi C,Suzuki Y,Shibuya M,Sugita K,Masuzawa-Ito K,Asano M

    更新日期:1992-04-01 00:00:00

  • AT-1015, a novel serotonin (5-HT)2 receptor antagonist, blocks vascular and platelet 5-HT2A receptors and prevents the laurate-induced peripheral vascular lesion in rats.

    abstract::The serotonin (5-HT2A) antagonistic activities and the protective effect on laurate-induced peripheral vascular lesions of AT-1015, a novel 5-HT2 receptor antagonist, were investigated. In platelet aggregation, AT-1015 selectively inhibited in vitro 5-HT2A receptor-mediated aggregation, and the activity was almost equ...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/00005344-200004000-00002

    authors: Kihara H,Hirose K,Koganei H,Sasaki N,Yamamoto H,Kimura A,Nishimori T,Shoji M,Yoshimoto R

    更新日期:2000-04-01 00:00:00

  • Local administration of lactic acid and a low dose of the free radical scavenger, edaravone, alleviates myocardial reperfusion injury in rats.

    abstract::The effects of local myocardial administration of lactic acid and low-dose edaravone were investigated to determine if this combination provides benefits similar to mechanical postconditioning. We randomly divided 108 rats into 6 groups: sham, reperfusion injury, postconditioning (Post), lactic acid (Lac), low-dose ed...

    journal_title:Journal of cardiovascular pharmacology

    pub_type: 杂志文章

    doi:10.1097/01.fjc.0000432860.48345.9d

    authors: Zhang G,Sun Y,Wang Y,Li X,Li T,Su S,Xu L,Shen H

    更新日期:2013-10-01 00:00:00