Effects of SA7060,a Novel Dual Inhibitor of Neutral Endopeptidase and Angiotensin-Converting Enzyme, on Deoxycorticosterone Acetate-Salt-Induced Hypertension in Rats
スポンサーリンク
概要
- 論文の詳細を見る
We evaluated whether a novel dual inhibitor of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), SA7060,(S)-2-[3-[(S)-2-(butoxycarbonyl)-2-hydroxyethyl]-3-isobutylureido]-3-(2-naphtyl) propionic acid, prevents deoxycorticosterone acetate (DOCA)-salt-induced hypertension and related organ damage, such as cardiovascular hypertrophy, renal dysfunction and renal tissue injury in rats. The effectiveness was compared with candoxatril and enalapril, which are a selective NEP and ACE inhibitor, respectively. During DOCA-salt treatment for 4 weeks, the rats were given SA7060,candoxatril, enalapril or vehicle, once daily by gavage. The 4-weeks treatment with DOCA and salt produced progressive increases in systolic blood presure. Daily administration of SA7060,candoxatril or enalapril significantly suppressed the development of hypertension induced by DOCA and salt, although the effect of enalapril was less potent at 4-weeks of the treatment period. In vehicletreated DOCA-salt rats, decreases in creatinine clearance and increases in urinary excretion of protein and blood urea nitrogen were observed. This funcitonal damage was improved most efficiently by the treatment with SA7060. There were significant increases in urinary excretions of atrial natriuretic peptide and cyclic GMP in SA7060- or candoxatril-treated animals. Histopathological examination of the kidney in DOCA-salt rats revealed tubular, glomerular and vascular lesions, all of which were improved in animals given SA7060 or candoxatril. When the vascular hypertrophy of the aorta was evaluated, there were significant increases in wall thickness, wall area and the wall-to-lumen ratio in vechicle-treated DOCA-salt rats compared with the sharm rats. The development of vascular hypertrophy was suppressed by the treatment with SA7060,candoxatril or enalapril. Our findings indicate that SA7060 efficiently prevents DOCA-salt-induced hypertension and related tissue injury, mainly by inhibiting NEP. Thus, SA7060 may be useful for treatment of both renin-dependent and renin-independent hypertensive subjects, although further studies examining efficiency in a renin-dependent hypertensive model are needed.
- 公益社団法人日本薬学会の論文
- 2000-07-01
著者
-
Matsumura Yasuo
Department Of Mechanical Physics Kyoto University
-
Nose Masafumi
Development Research Division Santen Pharmaceutical Co. Ltd.
-
Kuro Toshihiko
Department Of Pharmacology Osaka University Of Pharmaceutical Sciences
-
Ikuse Toshimi
Development Research Division Santen Pharmaceutical Co. Ltd.
-
OKAHARA Akihiko
Development Research Division, Santen Pharmaceutical Co., Ltd.,
-
Okahara Akihiko
Development Research Division Santen Pharmaceutical Co. Ltd.
関連論文
- Antihypertensive Effect of Sesamin. III. Protection against Development and Maintenance of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats
- EFFECTS OF PINACIDIL ON RENAL HEMODYNAMICS AND FUNCTION IN ANESTHETIZED DOGS
- EFFECTS OF TINORIDINE ON LIPID PEROXIDATION AND RENIN RELEASE IN THE RAT RENIN GRANULE FRACTION
- EFFECTS OF ALPHA-ADRENOCEPTOR AGONISTS ON RENIN RELEASE FROM RAT KIDNEY CORTICAL SLICES
- Chronic Hypoxia Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Knockout Mice
- Selective Endothelin ET_B Receptor Antagonist Improves Left Ventricular Function but Exaggerates Degeneration of Cardiomyocytes in J2N-k Hamsters
- Effects of Dietary Arachidonic Acid Supplementation on Age-Related Changes in Endothelium-Dependent Vascular Responses
- STIMULANT EFFECTS OF W-7,A CALMODULIN-ANTAGONIST, ON RENIN RELEASE FROM RAT KIDNEY CORTICAL SLICES
- STIMULATION OF RENIN RELEASE FROM RAT KIDNEY CORTICAL SLICES BY VITAMIN E-DEFICIENCY
- EFFECTS OF VITAMIN E DEPLETION AND REPLETION ON RENIN RELEASE FROM RENIN GRANULES
- EFFECT OF VITAMIN E-DEFICIENCY ON RENIN RELEASE FROM RENIN GRANULES
- Selective Antagonism of the ET_A Receptor, but Not the ET_B Receptor, Is Protective Against Ischemic Acute Renal Failure in Rats
- Antihypertensive Effect of Angiotensin I-Converting Enzyme Inhibitory Peptides from a Sesame Protein Hydrolysate in Spontaneously Hypertensive Rats
- Xanthoangelol D Isolated from the Roots of Angelica keiskei Inhibits Endothelin-1 Production through the Suppression of Nuclear Factor-κB(Pharmacology)
- Dietary Supplementation of L-Carnosine Prevents Ischemia/Reperfusion-Induced Renal Injury in Rats(Pharmacology)
- Effects of Sesamin on Aortic Oxidative Stress and Endothelial Dysfunction in Deoxycorticosterone Acetate-Salt Hypertensive Rats (Pharmacology)
- Antihypertensive Effect of Sesamin. IV. Inhibition of Vascular Superoxide Production by Sesamin
- Preventive Effect of a Chicken Extract on the Development of Hypertension in Stroke-prone Spontaneously Hypertensive Rats(Food & Nutrition Science)
- Antihypertensive Effects of Chicken Extract against Deoxycorticosterone Acetate-Salt-Induced Hypertension in Rats
- Endothelin ET_B Receptor-Mediated Action on Systemic and Renal Hemodynamics and Urine Formation in Deoxycorticosterone Acetate-Salt-Induced Hypertensive Rats
- Electron Captute Cross Sections of H(2p) Level in the Intermadiate Velocity Regime of H^+_-Na(3s),Na(3p) Collisions
- Behaviors of Excitation Cross Sections in the Intermediate Velocity Regime on Ion-Atom Collisions
- Selective Antagonism of Endothelin ET_A or ET_B Receptor in Renal Hemodynamics and Function of Deoxycorticosterone Acetate-Salt-Induced Hypertensive Rats
- Effects of Pre- and Post-ischemic Treatments with FK409, a Nitric Oxide Donor, on Ischemia/Reperfusion-Induced Renal Injury and Endothelin-1 Production in Rats(Pharmacology)
- Preventive Effect of Flavangenol on Ischemia/Reperfusion-Induced Acute Renal Failure in Rats(Pharmacology)
- Role of Endogenous Angiotensin II in Renal Hemodynamic and Excretory Responses to L-Arginine Infusion
- RENIN RELEASE AND LIPID PEROXIDATION BY ASCORBIC ACID IN THE RENIN GRANULE FRACTION OF RAT KIDNEY CORTEX
- Effects of the Endothelin ET_A-Receptor Antagonist FR139317 on Development of Hypertension and Cardiovascluar Hypertrophy in Deoxycorticosterone Acetate-Salt Hypertensive Rats
- Tempol Protects against Ischemic Acute Renal Failure by Inhibiting Renal Noradrenaline Overflow and Endothelin-1 Overproduction(Pharmacology)
- A Nuclear Factor-κB Inhibitor BAY 11-7082 Suppresses Endothelin-1 Production in Cultured Vascular Endothelial Cells
- Involvement of Proteasome in Endothelin-1 Production in Cultured Vascular Endothelial Cells
- Protective Effect of SM-19712, a Novel and Potent Endothelin Converting Enzyme Inhibitor, on Ischemic Acute Renal Failure in Rats
- Protective Effect of KB-R7943, a Novel Na^+/Ca^ Exchange Inhibitor, on Ischemic Acute Renal Failure in Rats
- Effects of Sesamin on Altered Vascular Reactivity in Aortic Rings of Deoxycorticosterone Acetate-Salt-Induced Hypertensive Rat
- Effects of SA7060,a Novel Dual Inhibitor of Neutral Endopeptidase and Angiotensin-Converting Enzyme, on Deoxycorticosterone Acetate-Salt-Induced Hypertension in Rats
- EFFECTS OF LABETALOL ON RENIN RELEASE FROM RAT KIDNEY CORTICAL SLICES
- 2 Biosynthesis of Endothelin-1 (ET-1) and its Pathophysiological Roles(The Role of the Endothelin System in Cardiovascular Diseases, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- Effects of 3-amino-1,2,4-triazole on plasma renin activity and renal peroxisomal enzymes in rats.
- Inhibitory effects of nisoldipine and saralasin on angiotensin II-induced antidiuresis in anesthetized dogs.
- Effects of CV-4093, a new dihydropyridine calcium channel blocker, on renal hemodynamics and function in strke-prone spontaneously hypertensive rats(SHRSP).
- Effects of W-7 and W-5 on renin release from rat kidney cortical slices.
- Diuretic effects of L-threo-3,4-dihydroxyphenylserine(L-threo-DOPS) in anesthetized rats.