The role of nitric oxide in the regulation of glomerular haemodynamics in humans
Christian Delles,Arnfried U. Klingbeil,Markus P. Schneider,Renate Handrock,Tim Schäufele,Roland E. Schmieder +5 more
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No plays an important role in the regulation of human glomerular haemodynamics, probably with a greater contribution to afferent than to efferent arteriolar tone in man.Abstract:
Background. According to experimental data, the afferent glomerular arteriole is particularly under control of nitric oxide (NO). By use of pharmacological manoeuvres, we examined whether this finding holds true in the human renal circulation in vivo. Methods. Seventy-seven volunteers (aged 50±9 years) with mild to moderate essential hypertension (n ¼ 57) or arterial normotension (n ¼ 20) were examined. Basal NO activity in the renal circulation was assessed by the change of renal plasma flow (RPF) through systemic infusion of the NO synthase inhibitor, N G -monomethyl-L-arginine (L-NMMA; 4.25 mg/kg). Hypertensive patients were treated over 8 weeks with either the calcium-channel blocker amlodipine or the AT1-receptor blocker valsartan, primarily dilating the afferent and efferent arteriole, respectively. Subsequently, renal haemodynamics and NO activity in the renal circulation were determined again. Results. L-NMMA reduced RPF in normotensive (by 57±70 ml/min/1.73 m 2 ; P<0.01) and hypertensive subjects (by 46±56 ml/min/1.73 m 2 ; P<0.001) with no significant difference between the two groups. The decrease of RPF through L-NMMA was closely related with the glomerular filtration rate (GFR; r ¼ 0.39, P<0.001). Administration of amlodipine increased GFR by 7.1±12.1 ml/min/1.73 m 2 ;( P<0.01) and in parallel reduced the response of RPF to L-NMMA to 19±48 ml/min/1.73 m 2 ;( P<0.05). In contrast, valsartan maintained GFR and left the response of RPF to L-NMMA unchanged. Conclusions. NO plays an important role in the regulation of human glomerular haemodynamics, probably with a greater contribution to afferent than to efferent arteriolar tone in man.read more
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References
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Edmond J Lewis,Lawrence G. Hunsicker,William R. Clarke,Tomas Berl,Marc A. Pohl,Julia B. Lewis,Eberhard Ritz,Robert C. Atkins,Richard D. Rohde,Itamar Raz +9 more
TL;DR: The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes, independent of the reduction in blood pressure it causes.
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Microalbuminuria Reduction With Valsartan in Patients With Type 2 Diabetes Mellitus A Blood Pressure–Independent Effect
TL;DR: For the same level of attained BP and the same degree of BP reduction, valsartan lowered UAER more effectively than amlodipine in patients with type 2 diabetes and microalbuminuria, including the subgroup with baseline normotension, which indicates a BP-independent antiproteinuric effect of vALSartan.
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Topography of nitric oxide synthesis by localizing constitutive NO synthases in mammalian kidney
TL;DR: The distinct location of both NOS isoforms in the cortex confirms that NO plays a crucial role in local glomerular signaling events in various animal species including humans.
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Glomerular actions of nitric oxide
Leopoldo Raij,Chris Baylis +1 more
TL;DR: The physiology and pathophysiology of NO in the kidney will lead to the development of new therapeutic avenues and increased NO production may be involved in the early pathogenic hemodynamic changes in diabetes and in the physiologic hemodynamic responses to normal pregnancy.
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Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality.
Robert J. Nijveldt,T. Teerlink,B. Van Der Hoven,M.P.C. Siroen,D.J. Kuik,J.A. Rauwerda,P.A.M. van Leeuwen +6 more
TL;DR: In critically ill patients, plasma ADMA concentration is a strong and independent risk factor for ICU mortality, and hepatic dysfunction is the most prominent determinant ofADMA concentration in this population.