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Losartan decreases vasopressin-mediated cAMP accumulation in the thick ascending limb of the loop of Henle in rats with congestive heart failure

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Abstract:

Abstract Introduction: 

Vasopressin (AVP) stimulates sodium reabsorption and Na,K,2Cl-cotransporter (NKCC2) protein level in the thick ascending limb (TAL) of Henle's loop in rats. Rats with congestive heart failure (CHF) have increased protein level of NKCC2, which can be normalized by angiotensin II receptor type-1 (AT1) blockade with losartan. Aim: 

In this study, we investigated whether CHF rats displayed changes in AVP stimulated cAMP formation in the TAL and examined the role of AT1 receptor blockade on this system. Method: 

CHF was induced by ligation of the left anterior descending coronary artery (LAD). SHAM-operated rats were used as controls. Half of the rats were treated with losartan (10 mg kg day−1 i.p.). Results: 

CHF rats were characterized by increased left ventricular end diastolic pressure. Measurement of cAMP in isolated outer medullary TAL showed that both basal and AVP (10−6 m) stimulated cAMP levels were significantly increased in CHF rats (25.52 ± 4.49 pmol cAMP g−1 protein, P < 0.05) compared to Sham rats (8.13 ± 1.14 pmol cAMP g−1 protein), P < 0.05). Losartan significantly reduced the basal level of cAMP in CHF rats (CHF: 12.56 ± 1.93 fmol g−1 protein vs. Los-CHF: 7.49 ± 1.08, P < 0.05), but not in Sham rats (SHAM: 4.66 ± 0.59 vs. Los-SHAM: 4.75 ± 0.71). AVP-mediated cAMP accumulation was absent in both groups treated with losartan (Los-SHAM: 4.75 ± 0.71 and Los-CHF: 7.49 ± 1.08). Conclusion: 

The results indicate that the increased NKCC2 protein level in the mTAL from CHF rats is associated with increased cAMP accumulation in this segment. Furthermore, the finding that AT1 receptor blockade prevents AVP-mediated cAMP accumulation in both SHAM and CHF rats suggests an interaction between angiotensin II and AVP in regulation of mTAL Na reabsorption.

Keywords: AT1 receptor; Na,K,2Cl-cotransporter; V2 receptor; receptor crosstalk

Document Type: Research Article

DOI: https://doi.org/10.1111/j.1748-1716.2007.01722.x

Affiliations: 1:  Department of Pharmacology, University of Copenhagen, Copenhagen N, Denmark 2:  The Water and Salt Research Center, Institute of Anatomy, University of Aarhus, Aarhus C, Denmark

Publication date: 2007-08-01

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