the patients in the african - heritage ( n = 9 ) and caucasian - heritage ( n = 11 ) groups had similar distributions of sex , age , and duration of diabetes ( male 75 vs. 70% , p = 0.89 ; mean  sd age 53.3  7.2 vs. 55.2  4.6 years , p = 0.50 ; and duration 10.3  10.7 vs. 6.8  6.4 years , p = 0.37 , respectively ) . systolic blood pressure and diastolic blood pressure were 124.4 vs. 122.1 mmhg ( p = 0.75 ) and 77.0 vs. 76.1 mmhg ( p = 0.81 ) , respectively . the patients were nave to antihypertensive therapy , and equal numbers in each group received metformin ( n = 6 ) and insulin ( n = 2 ) . a1c and urinary albumin were measured by high - pressure liquid chromatography ( ha 8 - 121 ; biomen , berkshire , u.k . ) and immunoturbidimetry , respectively . microalbuminuria was excluded on the basis of three consecutive albumin - to - creatinine ratios <3 mg / mmol in sterile , early - morning urine samples and a urinary albumin excretion rate < 30 mg / day . renal plasma flow ( rpf ) was measured by the constant infusion method ( 6,7 ) . a bolus dose of 8 mg / kg paraminohippurate ( merck , sharp & dohme , hoddesdon , u.k . ) was given with a 20 mg / min infusion . after a 90-min equilibration period , the concentration of the infusate was multiplied by the infusion flow rate and divided by the mean of duplicate plasma samples at this and subsequent time points . plasma paraminohippurate was assayed after deproteinizing the samples with 6% trichloroacetic acid for 10 min at 70c and sequentially adding sodium nitrite , ammonium sulfamate , and n-1-naphthylethylenediamine using a cobas mira ( roche , lewes , u.k . ) . after initial equilibration , an amino acid mixture ( vamin ; pharamcia & upjohn , milton keynes , u.k . ) was infused ( 0.043 ml  kg  min ) . rpf was assessed 80 min later , and then l - nmma ( clinalfa , laufelfingen , switzerland ) was begun at the nonpressor dose of 20 g  kg  min . both infusions were continued for a further 20 min , after which a final rpf measurement was made . during the studies , blood pressure was monitored automatically ( dinamap ; critikon , basingstoke , u.k . ) , and whole blood was sampled from a venflon in a hand vein to measure glucose by the oxidase method ( one touch ; lifescan , high wycombe , u.k . ) every 10 min . mean arterial pressure ( map ) was calculated as the diastolic blood pressure plus one - third of the pulse pressure . renal blood flow ( rbf ) was calculated by dividing the rpf by 1 hematocrit and renal vascular resistance ( rvr ) by dividing map by rbf . the study was approved by the ethics committee of the whittington hospital national health service trust . analyses between or within the groups were performed using spss for windows ( version 10 ; spss , chicago , il ) . continuous variables were compared with parametric or nonparametric tests and associations tested with spearman 's rank correlation test or pearson 's x test according to their distribution . categorical variables were compared using a  test with continuity correction or fisher 's exact test . clearance and rpf measurements were corrected for a body surface area of 1.73 m. data are expressed as means  sd unless otherwise stated . analyses between or within the groups were performed using spss for windows ( version 10 ; spss , chicago , il ) . continuous variables were compared with parametric or nonparametric tests and associations tested with spearman 's rank correlation test or pearson 's x test according to their distribution . categorical variables were compared using a  test with continuity correction or fisher 's exact test . clearance and rpf measurements were corrected for a body surface area of 1.73 m. data are expressed as means  sd unless otherwise stated . comparative baseline measurements of rpf and systolic and diastolic blood pressures were similar between the african - heritage and caucasian - heritage groups ( rpf 533.7  174.7 vs. 565.3  260.8 ml / min per 1.73 m , p = 0.78 ; systolic 124.9  23.7 vs. 121.6  12.3 mmhg , p = 0.29 ; and diastolic 77.1  9.5 vs. 76.3  5.7 mmhg , p = 0.81 , respectively ) . there were no differences in creatinine clearance or median urinary albumin excretion rate ( 93.7  19.9 vs. 98.9  19.5 ml / min per 1.73 m , p = 0.57 , and 12.6 [ 4.125.0 ] vs. 14.0 [ interquartile range 8.524.1 ] mg / day , p = 0.79 ) . averaged blood glucose was similar ( 6.7  0.9 vs. 7.4  0.9 mmol / l ; p = 0.14 ) . a1c was lower in the african - heritage than in the caucasian - heritage group ( 6.8  0.69 vs. 8.0  0.94% ; p = 0.005 ) . the l - nmma infusion was associated with significant changes in systolic blood pressure in the african - heritage group ( fig . relative to the baseline and post  amino acid measurements , there was a mean rise of 10.0 mmhg ( 95% ci 2.317.9 ; p = 0.017 ) and 7.3 mmhg ( 1.013.7 ; p = 0.03 ) , respectively , in the african - heritage group and 4.3 mmhg ( 1.8 to 10.4 ; p = 0.23 ) and 2.4 mmhg ( 3.5 to 8.3 ; p = 0.38 ) in the caucasian - heritage group . final blood pressure was higher in the african - heritage group ( 137.5  9.0 vs. 123.4  14.2 mmhg ; p < 0.05 ) and was associated with a fall in rbf ( 46.0 ml / min per 1.73 m ; p < 0.05 ) and a rise in rvr ( from 0.12  0.06 to 0.14  0.04 mmhg ml / min per 1.73 m ; p = 0.036 ) . the changes in rvr correlated with map ( r = 0.77 ; p = 0.004 ) . in this study , patients without hypertension or renal disease of african heritage had an increased sensitivity to the renal vasoconstrictive effect of no synthase ( nos ) inhibition . these data suggest that a reduction in no bioavailability may adversely affect autoregulatory processes that could potentially increase vulnerability to renal damage ( 8) . we used the amino acid infusion to optimize renal blood flow and suppress tubuloglomerular feedback as a contributor to vasoconstriction . therefore , the reduction in renal blood flow that we observed was probably due to an effect of nos inhibition on the renovascular smooth muscle . early in the course of diabetes , no production is necessary to forestall a rise in blood pressure . hypertension is associated with the generation of no - quenching free radicals and is a prerequisite for the development of renal disease ( 1012 ) . furthermore , the renal expression of nos in patients with diabetes is related to the degree of vasculopathy ( 13 ) . it could therefore be considered that upregulation of no production in patients of african heritage is related to a mechanism that opposes an enhanced vasoconstrictor tendency . although consistent with experimental studies , these outcomes require caution before being generalized . confirmatory studies in patients with and without diabetes with greater power and the evaluation of the role of vasoconstrictive cytokines , angiotensin
objective  we compared the renal and systemic vascular ( renovascular ) response to a reduction of bioavailable nitric oxide ( no ) in type 2 diabetic patients without nephropathy and of african and caucasian heritage.research design and methods  under euglycemic conditions , renal blood flow was determined by a constant infusion of paraminohippurate and changes in blood pressure and renal vascular resistance estimated before and after an infusion of l-ng-monomethyl-l-arginine.resultsin the african - heritage group , there was a significant fall in renal blood flow ( 46.0 ml / min per 1.73 m2 ; p < 0.05 ) and rise in systolic blood pressure ( 10.0 mmhg [ 95% ci 2.317.9 ] ; p = 0.017 ) , which correlated with an increase in renal vascular resistance ( r2 = 0.77 ; p = 0.004).conclusions  the renal vasoconstrictive response associated with no synthase inhibition in this study may be of relevance to the observed vulnerability to renal injury in patients of african heritage .