Non-Bone Marrow Origin of Neointimal Smooth Muscle Cells in Experimental In-Stent Restenosis in Rats

BackgroundRenal failure aggravates pathological cardiac remodelling induced by myocardial infarction (MI). Cardiac remodelling is associated with telomere shortening, a marker for biological ageing. We investigated whether mild and severe renal failure shorten cardiac telomeres and excessively shorten telomeres after MI.MethodsRats were subjected to sham, unilateral (UNX) or 5/6th nephrectomy (5/6NX) to induce none, mild or severe renal failure. MI was induced by left coronary artery ligation. Renal function parameters and blood pressure were measured. DNA was isolated from non-infarcted cardiac tissue. Telomere length was assessed by quantitative polymerase chain reaction (PCR).ResultsProteinuria was unchanged in UNX and MI compared with control, but strongly increased in 5/6NX, UNX+MI and 5/6NX+MI. Serum creatinine levels were increased fourfold in 5/6NX and tenfold in 5/6NX+MI. 5/6NX and groups with both renal failure and MI showed an approximate 20% reduction of telomere length, similar to the MI group. No excess telomere shortening was observed in hearts from rats with renal ablation after MI.ConclusionSevere renal failure, but not mild renal failure, leads to shortening of cardiac telomeres to a similar extent as found after MI. Renal failure did not induce excessive telomere shortening after MI. (Neth Heart J 2009;17:190–4.

The role of angiotensin(1–7) in renal vasculature of the rat

Objective Angiotensin(1–7) is an active component of the renin–angiotensin–aldosterone system. Its exact role in renal vascular function is unclear. We therefore studied the effects of angiotensin(1–7) on the renal vasculature in vitro and in vivo.Methods Isolated small renal arteries were studied in an arteriograph system by constructing concentration–response curves to angiotensin II, without and with angiotensin(1–7). In isolated perfused kidneys, the response of angiotensin II on renal vascular resistance was measured without and with angiotensin(1–7). The influence of angiotensin(1–7) on angiotensin II-induced glomerular afferent and efferent constriction was assessed with intravital microscopy in vivo under anaesthesia. In freely moving rats, we studied the effect of angiotensin(1–7) on angiotensin II-induced reduction of renal blood flow with an electromagnetic flow probe.Results Angiotensin(1–7) alone had no effect on the renal vasculature in any of the experiments. In vitro, angiotensin(1–7) antagonized angiotensin-II-induced constriction of isolated renal arteries (9.71 ± 1.21 and 3.20 ± 0.57%, for control and angiotensin(1–7) pre-treated arteries, respectively; P < 0.0005). In isolated perfused kidneys, angiotensin(1–7) reduced the angiotensin II response (100 ± 16.6 versus 72.6 ± 15.6%, P < 0.05) and shifted the angiotensin II dose–response curve rightward (pEC50, 6.69 ± 0.19 and 6.26 ± 0.12 for control and angiotensin(1–7) pre-treated kidneys, respectively; P < 0.05). Angiotensin(1–7), however, was devoid of effects on angiotensin-II-induced constriction of glomerular afferent and efferent arterioles and on angiotensin-II-induced renal blood flow reduction in freely moving rats in vivo.Conclusion Angiotensin(1–7) antagonizes angiotensin II in renal vessels in vitro, but does not appear to have a major function in normal physiological regulation of renal vascular function in vivo

Non-Bone Marrow Origin of Neointimal Smooth Muscle Cells in Experimental In-Stent Restenosis in Rats

BackgroundRenal failure aggravates pathological cardiac remodelling induced by myocardial infarction (MI). Cardiac remodelling is associated with telomere shortening, a marker for biological ageing. We investigated whether mild and severe renal failure shorten cardiac telomeres and excessively shorten telomeres after MI.MethodsRats were subjected to sham, unilateral (UNX) or 5/6th nephrectomy (5/6NX) to induce none, mild or severe renal failure. MI was induced by left coronary artery ligation. Renal function parameters and blood pressure were measured. DNA was isolated from non-infarcted cardiac tissue. Telomere length was assessed by quantitative polymerase chain reaction (PCR).ResultsProteinuria was unchanged in UNX and MI compared with control, but strongly increased in 5/6NX, UNX+MI and 5/6NX+MI. Serum creatinine levels were increased fourfold in 5/6NX and tenfold in 5/6NX+MI. 5/6NX and groups with both renal failure and MI showed an approximate 20% reduction of telomere length, similar to the MI group. No excess telomere shortening was observed in hearts from rats with renal ablation after MI.ConclusionSevere renal failure, but not mild renal failure, leads to shortening of cardiac telomeres to a similar extent as found after MI. Renal failure did not induce excessive telomere shortening after MI. (Neth Heart J 2009;17:190–4.

The role of angiotensin(1–7) in renal vasculature of the rat

Objective Angiotensin(1–7) is an active component of the renin–angiotensin–aldosterone system. Its exact role in renal vascular function is unclear. We therefore studied the effects of angiotensin(1–7) on the renal vasculature in vitro and in vivo.Methods Isolated small renal arteries were studied in an arteriograph system by constructing concentration–response curves to angiotensin II, without and with angiotensin(1–7). In isolated perfused kidneys, the response of angiotensin II on renal vascular resistance was measured without and with angiotensin(1–7). The influence of angiotensin(1–7) on angiotensin II-induced glomerular afferent and efferent constriction was assessed with intravital microscopy in vivo under anaesthesia. In freely moving rats, we studied the effect of angiotensin(1–7) on angiotensin II-induced reduction of renal blood flow with an electromagnetic flow probe.Results Angiotensin(1–7) alone had no effect on the renal vasculature in any of the experiments. In vitro, angiotensin(1–7) antagonized angiotensin-II-induced constriction of isolated renal arteries (9.71 ± 1.21 and 3.20 ± 0.57%, for control and angiotensin(1–7) pre-treated arteries, respectively; P < 0.0005). In isolated perfused kidneys, angiotensin(1–7) reduced the angiotensin II response (100 ± 16.6 versus 72.6 ± 15.6%, P < 0.05) and shifted the angiotensin II dose–response curve rightward (pEC50, 6.69 ± 0.19 and 6.26 ± 0.12 for control and angiotensin(1–7) pre-treated kidneys, respectively; P < 0.05). Angiotensin(1–7), however, was devoid of effects on angiotensin-II-induced constriction of glomerular afferent and efferent arterioles and on angiotensin-II-induced renal blood flow reduction in freely moving rats in vivo.Conclusion Angiotensin(1–7) antagonizes angiotensin II in renal vessels in vitro, but does not appear to have a major function in normal physiological regulation of renal vascular function in vivo