Renoprotective effects of carvedilol in hypertensive‐stroke prone rats may involve inhibition of TGFβ expression

Abstract

1 The eect of carvedilol on renal function, structure and expression of TGFb and the matrix proteins ®bronectin, collagen I and collagen III, was evaluated in spontaneously hypertensive strokeprone (SHR-SP) rats fed a high fat, high salt diet. 2 Carvedilol treatment for 11 to 18 weeks did not alter systolic blood pressure in SHR-SP rats, however, it resulted in a signi®cant reduction in heart rate. 3 Carvedilol treatment reduced renal ®brosis and total, active and chronic renal damage to levels approaching those of WKY rats on a normal diet. 4 Urinary protein excretion was higher in SHR-SP rats (51+10 mg day 71 ) than WKY rats (18+2 mg day 71) and this was further increased when SHR-SP rats were fed a high fat, high salt diet (251+120 mg day 71). Treatment with carvedilol resulted in signi®cantly lower urinary protein excretion (37+15 mg day 71). 5 The expression of TGFb mRNA was signi®cantly higher in SHR-SP rats compared to WKY rats and a further increase was observed when rats were fed a high fat, high salt diet. Renal TGFb expression was signi®cantly reduced by treatment with carvedilol. The expression of ®bronectin and collagen I and collagen III mRNA showed a pattern similar to that observed with TGFb mRNA expression. Collagen I mRNA expression followed a pattern similar to renal ®brosis. 6 These data indicate that carvedilol can provide signi®cant renal protection in the absence of any antihypertensive activity and that the mechanisms involved in this action may include reduced expression of pro®brotic factors such as TGFb.

Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension

“…Elevated plasma TGF-b concentrations were noted in patients with albuminuria in hypertension and diabetic nephropathy, whereas angiotensin receptor blockers and ACE inhibitors decreased its excretion. This indicates that hyperexpression of TGF-b is an indicator of promotion of vascular and renal disease (Esmatjes et al, 2001;Wong et al, 2001;Agarwal et al, 2002;Houlihan et al, 2002;Russo et al, 2002). Angiotensin II cooperates with endothelin and TGF-b to activate collagen type I gene, resulting in the increased formation of extracellular matrix protein in the renal cortex and aorta (Fakhouri et al, 2001).…”

Differential Effects of Carvedilol and Metoprolol on Renal Function in Patients With Heart Failure

“…25 In the present study carvedilol did not decrease eGFR in the patients with HF, whereas metoprolol significantly decreased eGFR. Therefore, we can conclude from the present results that carvedilol has more renoprotective effect than metoprolol in the treatment of HF, although we could not find any differences between metoprolol and carvedilol in terms of plasma norepinephrine, BNP, or lipid peroxide concentrations.…”

Beta-adrenoblockers of third generation as medicines for drug therapy of patients with chronic kidney disease

“…Назначение таким животным карведилола в течение 18 недель оказывало слабый антигипертензивный эффект, но снижало потерю белка с мочой более чем в 6,5 раза по сравнению с нелечеными крыса-ми. Одновременно карведилол способствовал нор-мализации морфологической картины повреждения клубочков и ПК, подавляя в почечной ткани гипер-экспрессию мРНК профибротического цитокина TGF-β и матриксных белков фибронектина и колла-генов I и III типов [7,36].…”