Endothelium-derived relaxing factor responses in Doca-salt hypertensive rats

Kirchner, K. A.; Scanlon, Peter H; Dzielak, David J.; Hester, Robert L.

doi:10.1152/ajpregu.1993.265.3.r568

Cited by 13 publications

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“…They concluded that the increased NO release resulted from a reduction in high blood pressure. Reduced release of endothelium-derived relaxing factor (NO) in the aorta has been demonstrated in DOCA hypertensive rats (37) . However, the reduction in MCVR in our study may not have been caused the increase in NO release, because we found no reduction in high blood pressure in DOCA hypertensive rats treated with candesartan cilexetil.…”

Section: Resultsmentioning

confidence: 99%

Chronic Angiotensin Blockade with Candesartan Cilexetil in DOCA/Salt Hypertensive Rats Reduces Cardiac Hypertrophy and Coronary Resistance without Affecting Blood Pressure.

et al. 1997

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To determine whether angiotensin II participates in the pathogenesis of cardiac hypertrophy and impairs coronary circulation in DOCA/salt hypertension, DOCA hypertensive rats were treated with candesartan cilexetil for 8 wk. DOCA/salt hypertension was induced in Wistar rats by removing the right kidney and subcutaneously injecting deoxycorticosterone acetate once a week. Control rats were given subcutaneous injections of saline and maintained on a normal diet. After 4 wk of observation, the angiotensin II receptor antagonist candesartan cilexetil was administered by oral gavage for 8 wk to 14 rats. Systolic blood pressure was measured weekly with the tail-cuff method. After 12 wk, the rats were killed and prepared. The isolated hearts were perfused by a Langendorff apparatus at constant flow. Perfusion pressure was measured by a small-volume transducer, and perfusion flow was recorded by a drop counter. Development of hypertension was not prevented by candesartan cilexetil treatment, but development of cardiac hypertrophy was inhibited. Minimum coronary vascular resistance (MCVR) obtained upon infusing adenosine into the isolated hearts was significantly higher in DOCA/salt hypertensive rats than in sham-operated controls. The elevated MCVR in DOCA/salt hypertensive rats was decreased by the administration of candesartan cilexetil for 8 wk. Thus, candesartan cilexetil regressed cardiac hypertrophy and improved coronary vascular resistance without affecting high blood pressure. These findings suggest that angiotensin II plays an important role in the pathogenesis of cardiac hypertrophy in DOCA/salt hypertension and that cardiac hypertrophy increases coronary vascular resistance. (Hypertens Res 1997; 20: 263-267) Key Words: DOCA/salt hypertension, rat, cardiac hypertrophy, coronary perfusion resistance, angiotensin II receptor antagonist, angiotensin Cardiac hypertrophy often results from hypertension, and ensuing left ventricular hypertrophy increases mortality from cardiovascular complications (1-3). Regression of cardiac hypertrophy usually occurs when blood pressure is lowered by antihypertensive therapy. Recent evidence indicates that the cardiac renin-angiotensin system contributes to the development of hypertrophy (4, 5). When angiotensin converting enzyme (ACE) inhibitors are given to spontaneously hypertensive rats (SHR), cardiac hypertrophy regresses, regardless of whether blood pressure is lowered (6-8) or not (9). The cardiac regression produced by ACE inhibitors may in part also be due to increased bradykinin level resulting from kininase inhibition (10). Angiotensin receptor antagonists developed recently for clinical use as antihypertensive drugs (11, 12) do not increase bradykinin. These drugs also cause cardiac hypertrophy to regress in hypertension (13-15), but it is not known whether this regression depends on blockade of angiotensin II. Accordingly, the present study aimed to determine whether chronic angiotensin blockade can cause regression of cardiac hypertrophy even without lowering high...

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Section: Resultsmentioning

confidence: 99%

Chronic Angiotensin Blockade with Candesartan Cilexetil in DOCA/Salt Hypertensive Rats Reduces Cardiac Hypertrophy and Coronary Resistance without Affecting Blood Pressure.

et al. 1997

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“…Basal production of NO and endothelium-dependent relaxation are attenuated in conduit arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. [5][6][7] However, the role of NO in regulating basal tone in small arteries of DOCA-salt rats has not been resolved. [7][8][9] Oxidative stress contributes to the pathogenesis of hypertension.…”

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confidence: 99%

Reduced NOS3 Phosphorylation Mediates Reduced NO/cGMP Signaling in Mesenteric Arteries of Deoxycorticosterone Acetate-Salt Hypertensive Rats

et al. 2004

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Abstract-Salt-sensitive hypertension is associated with impaired NO/cGMP signaling. We hypothesized that increased superoxide production by NADPH oxidase and altered endothelial NO synthase (NOS3) phosphorylation determine endothelial dysfunction in hypertension. Experiments tested if NO/cGMP signaling and NOS3 serine phosphorylation are decreased and NADPH oxidase activity is increased in mesenteric arteries from deoxycorticosterone acetate (DOCA)-salt rats compared with arteries from placebo rats. Concentration response curves to phenylephrine were performed in mesenteric arteries in the presence and absence of N-nitro-L-arginine (LNA) and antioxidants to determine the influence of basal NO and superoxide production on vascular tone. LNA increased phenylephrine sensitivity in arteries from placebo, but not DOCA-salt rats, regardless of antioxidant treatment. To determine basal cGMP production, mesenteric arteries were incubated with 3-isobutyl-1-methylxanthine in the presence or absence of LNA, sodium nitroprusside (SNP), antioxidants, or tetrahydrobiopterin. NOS-dependent cGMP production was reduced in arteries from DOCA-salt rats compared with arteries from placebo rats and was not restored by acute treatment with antioxidants or tetrahydrobiopterin. SNP-induced cGMP production was similar between groups as was NADPH oxidase activity, measured by lucigenin chemiluminescence, in mesenteric arteries. Expression and phosphorylation of NOS3 were examined by Western blotting. Phosphorylation of NOS3 was decreased in arteries from DOCA-salt rats compared with placebo at serine residues 1179 and 635. These findings indicate that diminished NO/cGMP signaling in mesenteric arteries from DOCA-salt rats is caused by reduced phosphorylation of NOS3 at serine 1179 and serine 635, rather than NO scavenging by superoxide. Key Words: mesenteric arteries Ⅲ cyclic GMP Ⅲ nitric oxide synthase Ⅲ phosphorylation Ⅲ deoxycorticosterone T he endothelium plays a critical role in maintaining vascular tone via the release of vasoactive substances, and endothelial dysfunction is associated with the development of hypertension. While the underlying mechanisms are not completely understood, decreased endothelium-derived nitric oxide (NO) may contribute to endothelial dysfunction. Decreased endothelial NO synthase (NOS3) expression or activity, 1 decreased NOS3 substrate or cofactor availability, 2-3 or increased degradation of NO by reactive oxygen species (ROS) 4 may all contribute to decreased NO bioavailability. Basal production of NO and endothelium-dependent relaxation are attenuated in conduit arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. 5-7 However, the role of NO in regulating basal tone in small arteries of DOCA-salt rats has not been resolved. [7][8][9] Oxidative stress contributes to the pathogenesis of hypertension. DOCA-salt hypertension is associated with increased production of superoxide (O 2 ·Ϫ ) via activation of NAD(P)H oxidase in conduit arteries. 6,10 O 2 ·Ϫ reacts rapidly with NO to form pe...

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“…2) Recent studies reported that the synthesis or release of endothelium-derived relaxing factor (EDRF) and responses to EDRF are impaired in this model of hypertension. 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: 63%

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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Endothelium-derived relaxing factor responses in Doca-salt hypertensive rats

Cited by 13 publications

References 0 publications

Chronic Angiotensin Blockade with Candesartan Cilexetil in DOCA/Salt Hypertensive Rats Reduces Cardiac Hypertrophy and Coronary Resistance without Affecting Blood Pressure.

Chronic Angiotensin Blockade with Candesartan Cilexetil in DOCA/Salt Hypertensive Rats Reduces Cardiac Hypertrophy and Coronary Resistance without Affecting Blood Pressure.

Reduced NOS3 Phosphorylation Mediates Reduced NO/cGMP Signaling in Mesenteric Arteries of Deoxycorticosterone Acetate-Salt Hypertensive Rats

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

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