Different Contributions of Endothelin-A and Endothelin-B Receptors in the Pathogenesis of Deoxycorticosterone Acetate–Salt–Induced Hypertension in Rats

Matsumura, Yasuo; Hashimoto, Norio; Taira, Shima; Kuro, Toshihiko; Kitano, Rika; Ohkita, Mamoru; Opgenorth, Terry J.; Takaoka, Masanori

doi:10.1161/01.hyp.33.2.759

Cited by 104 publications

(88 citation statements)

References 30 publications

(37 reference statements)

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“…Also, long-term treatment with the nonselective ET A /ET B antagonist bosentan attenuates the development of hypertension and vascular remodeling in DOCA-salt rats. Bosentan decreases the blood pressure to a degree similar to that observed with selective ET A receptor antagonist, suggesting that ET A receptors are the main receptors involved in the pathogenesis of DOCA-salt-sensitive hypertension [80].…”

Section: Effects Of Et Antagonists In Hypertensionsupporting

confidence: 55%

“…Thus, ET does not appear to release less vasorelaxant substances in hypertensive rats, and this may not be a mechanism via which ET contributes to the pathophysiology of hypertension. It has been proposed that ET A receptors may play a role in the development of DOCA-salt-induced hypertension, whereas ET B receptors may protect against vascular and renal injuries in this model [80]. However, other studies have provided opposite results, suggesting that ET may indeed release less endothelium-derived relaxing factor in SHR blood vessels [46].…”

Section: Vascular Response To Et In Hypertensionmentioning

confidence: 86%

“…These rather modest effects have suggested that ET involvement in hypertension is minor [66]. However, a recent study indicates that acute administration of the ET A antagonist ABT-627 to DOCA-salt rats produces significant hypotensive effect and that long-term treatment with this agent suppresses the development of hypertension [80]. Also, long-term treatment with the nonselective ET A /ET B antagonist bosentan attenuates the development of hypertension and vascular remodeling in DOCA-salt rats.…”

Section: Effects Of Et Antagonists In Hypertensionmentioning

confidence: 99%

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The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Hynynen

Khalil²

2006

PRC

102

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The discovery of endothelin two decades ago has now evolved into an intricate vascular endothelin (ET) system. Several ET isoforms, receptors, signaling pathways, agonists, antagonists, and clinical applications have been identified and documented in first-rate patents. The role of ET as one of the most potent endothelium-derived vasoconstricting factors is now complemented by a newly discovered role in vascular relaxation. ET synthesis is initiated by the transcription of ET genes in endothelial cells and the generation of the gene products preproET and big ET, which are further cleaved by specific ET converting enzymes into ET-1, -2, -3 and -4 isoforms. ET isoforms bind with different affinities to ET A and ET B2 receptors in vascular smooth muscle, and stimulate [Ca 2+ ] i , protein kinase C, mitogen-activated protein kinase and other signaling mechanisms of smooth muscle contraction, growth and proliferation. ET also binds to endothelial ET B1 receptors, which mediate the release of vasodilator substances such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor. Endothelial ET B1 receptors may also function in ET re-uptake and clearance. Although the effects of ET on vascular function and growth are well-recognized, the role of ET and its receptors in the regulation of blood pressure and in the pathogenesis of hypertension is not clearly established. Salt-dependent hypertension in experimental animals and some forms of moderate to severe hypertension in human may show elevated levels of plasma or vascular ET; however, other forms of hypertension show normal ET levels. The currently available ET receptor antagonists reduce blood pressure in some forms of experimental hypertension. Careful examination of recent patents may identify more effective and specific modulators of the vascular ET system for clinical use in human hypertension.

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Section: Effects Of Et Antagonists In Hypertensionsupporting

confidence: 55%

Section: Vascular Response To Et In Hypertensionmentioning

confidence: 86%

Section: Effects Of Et Antagonists In Hypertensionmentioning

confidence: 99%

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The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Hynynen

Khalil²

2006

PRC

102

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“…The pathophysiologic mechanisms underlying the development and maintenance of DOCA-salt hypertension include increased levels of arginine vasopressin [120], angiotensin-II/aldosterone [300,313], endothelin [179,204,258,302] and oxidative stress [154,175], excessive activation of the sympathetic nervous system [132] and nitric oxide synthase (NOS) uncoupling due to oxidative depletion of its cofactor tetrahydrobiopterin (BH4) [274]. Indeed, both inhibition of the angiotensin-aldosterone system and endothelin receptor blockade have been shown to prevent cardiac remodeling, even without concomitantly reducing arterial blood pressure [89,257].…”

Section: Doca-salt Ratsmentioning

confidence: 99%

Rodent models of heart failure: an updated review

et al. 2012

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Heart failure (HF) is one of the major health and economic burdens worldwide, and its prevalence is continuously increasing. The study of HF requires reliable animal models to study the chronic changes and pharmacologic interventions in myocardial structure and function and to follow its progression toward HF. Indeed, during the past 40 years, basic and translational scientists have used small animal models to understand the pathophysiology of HF and find more efficient ways of preventing and managing patients suffering from congestive HF (CHF). Each species and each animal model has advantages and disadvantages, and the choice of one model over another should take them into account for a good experimental design. The aim of this review is to describe and highlight the advantages and drawbacks of some commonly used HF rodents models, including both non-genetically and genetically engineered models, with a specific subchapter concerning diastolic HF models.

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“…3,4) In addition, we found the hypotensive effect of FR 139317 or ABT-627, both of which are selective endothelin ET A receptor antagonists , in DOCAsalt hypertensive rats, thereby suggesting that endothelin and ET A receptors are closely involved in the maintenance of DOCA-salt hypertension. 5,6) The mechanisms by which BEC prevents the development of DOCA-salt hypertension are unclear, but feeding with BEC for 5 weeks may affect the activities of the above neural and/or humoral factors.…”

Section: Discussionmentioning

confidence: 99%

Antihypertensive Effects of Chicken Extract against Deoxycorticosterone Acetate-Salt-Induced Hypertension in Rats.

Matsumura

Okui

Ono³

et al. 2001

Biological & Pharmaceutical Bulletin

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In some Asian regions, particularly in Chinese communities in Southeast Asia, Brand's Essence of Chicken (BEC) is used as a traditional health food for various purposes, including recovery from postpartum sickness, the physical development of athletes, recovery from mental stress and enhancement of the mental efficiency of students. 1) However, little is known as to whether the supplement of BEC has a beneficial effect against the development and progression of cardiovascular diseases such as hypertension. The present study was designed to evaluate whether a dietary supplement of BEC has a preventive effect in the development of experimental hypertension induced by deoxycorticosterone acetate (DOCA) and salt, which has been used extensively as a useful model of human hypertension. We report here that dietary BEC can markedly suppress the elevation of blood pressure, cardiovascular hypertrophy and renal damage in DOCA-salt hypertensive rats. MATERIALS AND METHODSMaterials BEC (70 ml/bottle, Cerebos Pacific, Ltd., Singapore) was freeze-dried, and the resultant powder (about 6 g from 1 bottle of BEC) was mixed with normal commercial diet (NMF, Oriental Yeast Co., Ltd.) at 0.1 w/w% (BEC-containing diet). A feeding of this diet (15-30 g/rat/d) is equal to a dosage of about 0.175-0.35 ml of BEC/rat/d, and corresponds to approximately half to one bottle of BEC/human/ day.Animal Experiments Male Sprague-Dawley rats (6 weeks old) were anesthetized with sodium pentobarbital (40 mg/kg, i.p.) and the right kidney was removed via a right flank incision. After a 1-week postsurgical recovery period, rats were separated into a sham-operated group and a DOCA-salt group. The latter was further separated into a normal diet group and a BEC-containing diet group. The sham group was fed a normal diet and tap water ad libitum. Rats of the DOCA-salt group were treated twice weekly with DOCA suspended in corn oil, which was administered subcutaneously (15 mg/kg), and 1% NaCl was added to their tap water for drinking. Systolic blood pressure (SBP) was monitored weekly by a tail cuff and a pneumatic pulse transducer (BP-98A, Softron, Tokyo, Japan). After 5 weeks, the animals were placed in metabolic cages, urine was collected overnight, and then all rats were bled from the abdominal aorta to obtain blood samples. The heart, left kidney and aorta were excised and weighed. The thoracic aorta and left kidney were used for morphometric analysis.Histological Studies The thoracic aorta and the left kidney of each rat was preserved in phosphate-buffered 10% formalin, after which the tissues were chopped into small pieces, embedded in paraffin, cut at 4 mm and stained with hematoxylin and eosin. Three different cross sections of each vessel placed under a microscope were photographed, and the vessel wall area and thickness were determined using an image analyzer (AE-6905C, ATTO, Tokyo).Statistical Analysis All values were expressed as meanϮS.E.M. For statistical analysis, we used one-way ANOVA followed by Tukey-Kramer multiple comparison tests. F...

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Different Contributions of Endothelin-A and Endothelin-B Receptors in the Pathogenesis of Deoxycorticosterone Acetate–Salt–Induced Hypertension in Rats

Cited by 104 publications

References 30 publications

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Rodent models of heart failure: an updated review

Antihypertensive Effects of Chicken Extract against Deoxycorticosterone Acetate-Salt-Induced Hypertension in Rats.

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