Handle region peptide counteracts the beneficial effects of the @entity3449 inhibitor aliskiren in spontaneously @entity101 XXXX .

@entity101 @entity17162 @entity1283 @entity1808 @entity3449 @entity1812 @entity35 @entity12168
To investigate whether the putative (pro) @entity3449 receptor blocker, the @entity12168 ( @entity12168 ), exerts effects on top of the blood pressure-lowering and cardioprotective effects of the @entity3449 inhibitor aliskiren, spontaneously @entity101 @entity35 were implanted with telemetry transmitters to monitor heart rate and mean arterial pressure (MAP). After a 2-week recovery period, vehicle, aliskiren, @entity12168 (100 and 1 mg/kg per day, respectively), and @entity12168 +aliskiren were infused for 3 weeks using osmotic minipumps. Subsequently, the heart was removed to study coronary function according to Langendorff. Baseline MAP and heart rate in vehicle-treated @entity35 were 146  3 mm Hg and 326  4 bpm. @entity12168 did not affect MAP, whereas aliskiren and @entity12168 +aliskiren lowered MAP (by maximally 29  2 and 20  1 mm Hg, respectively) without affecting heart rate. Aliskiren significantly reduced MAP throughout the 3-week infusion period, whereas the blood pressure-lowering effect of @entity12168 +aliskiren returned to baseline within 2 weeks of treatment. In comparison with vehicle, @entity17162 increased the endothelium-dependent response to @entity1812 and decreased the response to @entity1808 in the coronary circulation, whereas these responses were not altered after treatment with @entity12168 or @entity12168 +aliskiren. @entity12168 did not alter plasma @entity3449 activity, plasma angiotensin levels, or the renal angiotensin content, either alone or on top of aliskiren, nor did it alter the aliskiren-induced decrease in renal Ang II type 1 receptor expression. Yet, it did reverse the aliskiren-induced reduction in cardiomyocyte area, without affecting this area when given alone. In conclusion, @entity12168 counteracts the beneficial effects of aliskiren on blood pressure, coronary function, and @entity1283 in an angiotensin-independent manner.
