Effects of Enalapril, Losartan, and Verapamil on Blood Pressure and Glucose Metabolism in the Cohen-Rosenthal Diabetic Hypertensive Rat

Rosenthal, Talma; Erlich, Yael; Rosenmann, E.; Cohen, Arthur

doi:10.1161/01.hyp.29.6.1260

Cited by 31 publications

(9 citation statements)

References 50 publications

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“…In this study, the calcium channel blocker verapamil only partially prevented the increase in SBP induced by long-term administration of Ang II at a dose that was comparable to those that have been shown to prevent elevation of arterial pressure in different animal models of hypertension. 19,27,28 In line with previous observations, losartan abolished the Ang II-induced increase in SBP. 21 Whereas losartan prevented the Ang II-induced increases in local aortic ET-1 concentrations, verapamil had no effect on tissue levels of this peptide.…”

Section: Discussionsupporting

confidence: 83%

Losartan but Not Verapamil Inhibits Angiotensin II–Induced Tissue Endothelin-1 Increase

et al. 1998

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Abstract-Endothelin partially mediates angiotensin (Ang) II-induced vascular changes in vivo. This study investigated the effects of the angiotensin type 1 receptor antagonist losartan and the calcium channel blocker verapamil on vascular reactivity and tissue endothelin-1 levels in aortas of Wistar-Kyoto rats treated for 2 weeks with Ang II (200 ng ⅐ kg Ϫ1 ⅐ min Ϫ1). Ang II increased systolic blood pressure (39Ϯ4 mm Hg, PϽ0.05). Concomitant treatment with losartan abolished the Ang II-induced pressure increase (PϽ0.05), whereas verapamil reduced it only partially (PϽ0.05). In the aortas of rats with Ang II-induced hypertension, tissue endothelin-1 content was increased threefold and contractions to endothelin-1 were impaired (PϽ0.05). Interestingly, these alterations were normalized by losartan (PϽ0.05) but not by verapamil. Hence, there was a strong, negative correlation between contractions to endothelin-1 and tissue endothelin-1 content (rϭϪ0.733, PϽ0.0001). In contrast, both antihypertensive drugs normalized impaired endothelium-dependent relaxations to acetylcholine and reduced the sensitivity of vascular smooth muscle to sodium nitroprusside compared with Ang II-treated rats (PϽ0.05). Ang II-induced hypertension enhanced endotheliumdependent contractions to acetylcholine, and these were normalized by either drug. In conclusion, these findings suggest that long-term treatment with Ang II modulates endothelin-1 protein expression in the rat aorta. Although both antihypertensive agents lowered blood pressure and normalized endothelial function, only losartan prevented the increase in tissue endothelin-1 content, suggesting that angiotensin type 1 receptor antagonists but not calcium antagonists modulate tissue endothelin-1 in vivo. (Hypertension. 1998;31:1305-1310.) Key Words: angiotensin II Ⅲ endothelin Ⅲ endothelium Ⅲ losartan Ⅲ verapamil Ⅲ aorta A ngiotensin II is an important mediator contributing to cardiovascular diseases such as hypertension, congestive heart failure, and renal failure.1-3 Ang II has multiple effects as a local modulator of vascular tone in an autocrine and paracrine manner via specific angiotensin receptors.2 Ang II-induced proliferation of rat VSMCs is mediated via the AT 1 receptor. 4 Ang II also stimulates the release of relaxant factors such as NO [5][6][7] and constricting factors such as prostanoids 8 and ET-1 in endothelial cells. -11ET-1 is a potent vasoconstrictor peptide 1,9 and acts as a mitogen and trophic factor in cultured VSMCs.12,13 The Ang II-induced expression of pre-pro-ET mRNA and subsequent ET-1 synthesis occur not only in cultured vascular endothelial cells 9 -11,14 but also in nonendothelial cells such as rat VSMCs through its interaction with the AT 1 but not the AT 2 receptor. 15,16 Long-term treatment with Ang II increases tissue ET-1 content and induces vascular hypertrophy of small arteries, effects that are totally prevented by ET A receptor blockade, 17 suggesting that this interaction between the vascular renin-angiotensin system and ET-1 is also opera...

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Section: Discussionsupporting

confidence: 83%

Losartan but Not Verapamil Inhibits Angiotensin II–Induced Tissue Endothelin-1 Increase

et al. 1998

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“…On the other hand, its blockade of action or production has also been shown to result in diminution of proteinuria as well as slowing down of the progression of renal fibrosis in mice transgenic for HIV-1 [10, 11]. Similar results have been demonstrated in rat models of diabetes and hypertension [12, 13]. Moreover, the beneficial effects of Ang II inhibition have been reported in a variety of human renal diseases [14,15,16].…”

Section: Introductionmentioning

confidence: 73%

Angiotensin II Infusion Induces Nephrin Expression Changes and Podocyte Apoptosis

et al. 2008

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Background/Aim: In in vitro studies, angiotensin (Ang) II has been demonstrated to promote podocyte apoptosis. The present study evaluates the effects of Ang II infusion in rats on podocyte nephrin expression and apoptosis and the molecular mechanisms involved in Ang II-induced proteinuria and mesangial expansion. Methods: Sprague-Dawley rats were randomly assigned to receive either normal saline or Ang II (400 ng·kg^–1·min^–1) by means of a mini-osmotic pump for variable time periods. Systolic blood pressure and urinary protein and albumin excretion rate measurements were carried out on days 7, 14, 21, and 28. The animals were sacrificed on days 14 and 28 and evaluated for serum creatinine, renal pathological changes, podocyte apoptosis, renal nephrin mRNA, and protein expression. Results: The Ang II-infused rats developed hypertension and proteinuria. On day 14, the Ang II-infused rats showed narrowing of the slit diaphragm, an increase in podocyte nephrin mRNA and protein expression, and alterations in its distribution along the foot processes. On day 28, the Ang II-infused rats demonstrated the presence of apoptotic podocytes and decreased nephrin mRNA and protein expression. There was a negative correlation between nephrin expression and the numbers of apoptotic podocytes (r = –0.63, p < 0.05). Conclusion: These results suggest that changes in nephrin expression may play a role in the pathogenesis of Ang II-induced podocyte apoptosis.

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“…45 Furthermore, AT 1 blockade in hypertensive diabetic rats did not improve glucose metabolism. 46 In addition, in TG(mREN2)27 rats, blockade of AT 1 receptor did not increase IRS1/Akt phosphorylation. 47 As shown in Figure 5, one of the phenotypic changes observed in TGR is an increase in Akt phosphorylation.…”

Section: Santos Et Al Ang-(1-7) Improves Lipid and Glucose Metabolismmentioning

confidence: 90%

Improved Lipid and Glucose Metabolism in Transgenic Rats With Increased Circulating Angiotensin-(1-7)

Santos

Braga

Mario

et al. 2010

ATVB

151

126

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Objective-Obesity and diabetes remain among the world's most pervasive health problems. Although the importance of angiotensin II for metabolic regulation is well documented, the role of the angiotensin-(1-7)/Mas axis in this process is poorly understood. The aim of this study was to evaluate the effect of increased angiotensin-(1-7) plasma levels in lipid and glucose metabolism using transgenic rats that express an angiotensin-(1-7)-releasing fusion protein, TGR(A1-7)3292 (TGR). Methods and Results-The increased angiotensin-(1-7) levels in TGR induced enhanced glucose tolerance, insulin sensitivity, and insulin-stimulated glucose uptake. In addition, TGR presented decreased triglycerides and cholesterol levels, as well as a significant decrease in abdominal fat mass, despite normal food intake. These alterations were accompanied by a marked decrease of angiotensinogen expression and increased Akt in adipose tissue. Furthermore, augmented plasma levels and expression in adipose tissue was observed for adiponectin. Accordingly, angiotensin-(1-7) stimulation increased adiponectin production by primary adipocyte culture, which was blocked by the Mas antagonist A779. Circulating insulin and muscle glycogen content were not altered in TGR. Conclusion-These

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Effects of Enalapril, Losartan, and Verapamil on Blood Pressure and Glucose Metabolism in the Cohen-Rosenthal Diabetic Hypertensive Rat

Cited by 31 publications

References 50 publications

Losartan but Not Verapamil Inhibits Angiotensin II–Induced Tissue Endothelin-1 Increase

Losartan but Not Verapamil Inhibits Angiotensin II–Induced Tissue Endothelin-1 Increase

Angiotensin II Infusion Induces Nephrin Expression Changes and Podocyte Apoptosis

Improved Lipid and Glucose Metabolism in Transgenic Rats With Increased Circulating Angiotensin-(1-7)

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