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Our previous studies in rats with ablation nephrectomy have shown similar cardiorenal protective effects of renin-angiotensin system (RAS)-dependent treatment (combination of angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker) and RAS-independent treatment (combination of α- and β-adrenoreceptor antagonist and diuretics). Moreover, selective blockade of endothelin (ET) receptor type A (ETA) improved survival rate and attenuated hypertension and organ damage in Ren-2 transgenic rats. Therefore, we were interested in whether ETA receptor blockade could have additive effects to the classical blockade of the RAS. Transgenic rats underwent 5/6 renal ablation at the age of 2 months and were treated for 20 weeks with RAS blockers alone (angiotensin II receptor blocker – losartan, and angiotensin-converting enzyme inhibitor – trandolapril), ETA receptor blocker alone (atrasentan) or with the combination of RAS and ETA receptor blockade. RAS blockade normalized blood pressure and improved survival. It decreased cardiac hypertrophy and proteinuria as well as tissue angiotensin II and ET-1 levels. In contrast, ETA receptor blockade only partially improved survival rate, reduced blood pressure, attenuated the development of cardiac hypertrophy and transiently reduced proteinuria. However, no additive cardio- and renoprotective effects of ETA and RAS blockade were noted at the end of the study.

Background: There are only few studies documenting the long-term outcome of aorto-caval fistula (ACF) in rats, a model of volume overload heart failure (HF). The aim of the present study was to describe HF-related morbidity and mortality, and to examine the relation between cardiac hypertrophy and survival. Methods: Adult male Wistar rats underwent needle ACF or sham operation and 71 animals surviving the acute procedure with patent ACF were followed for 52 weeks. Results: By the end of the study, 72% of the ACF animals deceased and 82% developed HF signs. Of the HF rats, 65% died (median: 3 weeks after HF onset). Before death, body weight increased by 9% followed by a final drop. 28% ACF rats died suddenly, without preceding HF. Sudden death occurred earlier and in the rats with a trend to larger hearts (p = 0.07). In the whole ACF cohort, heart weight (heart weight/body weight ratio) was inversely associated with the length of survival (r = –0.51, p < 0.001). Conclusion: The median survival of ACF Wistar rats is 43 weeks, longer than reported in other rat strains. Increased heart weight is associated with higher mortality and a significant number of animals die suddenly.

Background: In the present study we evaluated plasma and kidney angiotensin II (ANG II) levels in female and male Ren-2 transgenic rats (TGR) in comparison to age-matched female and male normotensive Hannover Sprague-Dawley rats. Methods: The rats were maintained on a normal sodium (NS) diet (0.6% NaCl) or fed a high sodium (HS) diet (2% NaCl) for 4 days or were sodium depleted by administration of 40 mg furosemide per liter drinking water overnight followed by 3 days of low sodium diet (0.01% NaCl) (LS + F). ANG II levels were determined by radioimmunoassay. Results: Female TGR at the age of 38 days were already hypertensive and had developed cardiac hypertrophy, whereas male TGR at this age still exhibited a normotensive phenotype. HS diet increased the blood pressure (BP) but did not alter the ANG II levels in TGR at any age. LS + F decreased the BP without significant change in ANG II concentrations in TGR. Female TGR responded to salt loading and salt depletion by more pronounced changes in BP than male TGR. Conclusions: Female TGR develop hypertension more rapidly and the salt-sensitive component of hypertension is more pronounced in female than in male TGR.

Background/Aims: Since there are no data available so far on the role of renal cyclooxygenase-2 (COX-2) in hypertensive Ren-2-transgenic rats (TGR), in the present study we evaluated renal cortical COX-2 protein expression and prostaglandin E2 (PGE2) concentrations as well as renal functional responses to acute COX-2 inhibition in male heterozygous TGR and in normotensive Hannover Sprague-Dawley (HanSD) rats fed either a normal-sodium (NS) or a low-sodium (LS) diet. Methods: In rats fed either the NS or the LS diet for 12 days and prepared for clearance experiments with left ureteral catheterization, the renal functional responses of the left kidney were evaluated after intrarenal COX-2 inhibition with DuP-697 or NS-398. In renal cortical tissue, COX-2 protein expression was assessed by immunoblotting, and the concentration of PGE2 as a marker of COX-2 activity was determined by enzyme immunoassay. Mean arterial pressure in the right femoral artery was monitored by means of a pressure transducer. Results: In heterozygous TGR, to our surprise, the LS diet normalized the mean arterial pressure. Despite significantly higher renocortical expression of COX-2 and PGE2 concentrations as well as urinary PGE2 excretion in TGR as compared with HanSD rats kept on the NS diet, selective intrarenal COX-2 inhibition did not influence renal function either in TGR or in HanSD rats. The LS diet increased renocortical COX-2 expression and PGE2 concentrations as well as urinary PGE2 excretion significantly stronger in TGR than in HanSD rats. Regardless of these increases, the intrarenal COX-2 inhibition caused comparable decreases in glomerular filtration rate, in absolute and fractional sodium excretion, as well as in urinary PGE2 excretion in TGR and HanSD rats kept on the LS diet. Conclusions: The present data show that a LS diet normalizes the mean arterial pressure in heterozygous male TGR. This first study on the role of renal COX-2 in TGR also demonstrates that COX-2-derived vasodilatory prostanoids do not act as renal compensatory vasodilator and natriuretic substances in this model of hypertension.