Changes And Clinical Significance Of The L-arginine/nitric Oxide Pathway In The Platelets And Molecular Markers On The Surface Of Activated Platelets In The Older Patients With Hypertension

Objective The goal of this study was to investigate the changes and its clinical significance of the L-arginine/nitric oxide pathway in the platelets and molecular markers (P-Selectin and glycoprotein b/ a) on the surface of the activated platelets in the older patients with essential hypertension or complicated with angina or diabetes mellitus. Methods 15 healthy older volunteers(1 group),20 essential hypertension without complications(2 group),15 hypertension complicated with angina pectoris(5 group) and 15 hypertension complicated with diabetes mellitus(4 group) were collected from inpatients and outpatients .The expression of P-Selectin(CD62p) and glycoprotein b/ a(PAC-1) on the surface of activated platelets were analyzed by flow cytometric 3-color irnmunofluorescence.The changes of L-arginine transport, the activity of nitric oxide synthase(NOS) and the production of nitric oxide(NO) were measured by radioimmunoassay. Results (1) The production of NO in plasma and in platelets, activity of NOS and content of cGMP in platelets of 2, 3 and 4 group were all decreased compared with those in 1 group. (2)By Eadie-Hafstee plot analysis we found that the maxim umtransport velocity(Vmax) of L-3H arginine transport in 2,3, and 4 group were diminished compared with those in 1 group (5.91 ?.66, 5.96 0.82, 4.19 0.55 vs 8.40 1.01 p<0.01) .especially 4 group. No changes of Michael's constant (Km) of 2 and 3 group were found compared with that of 1 group. But Km of 4 group was increased statistically compared with that of other groups (20.43 1.89vs 14.63 2.07, 14.71 1.62, 15.06 128p<0.01) .The transport efficiency of 2,3 and 4 group were also decreased than that of 1 group (0.402 0.066, 0.396 0.048, 0.205 0.030 vs 0.574 0.104 p<0.01), especially4 group. (3)The positive percent and geomean fluorescence index of CD62p (CD62 % and MFI) expression in 3 and 4 group were higher than that in 1 and 2 group. The positive percent and geomean fluorescence index of PAC-1 (PAC-1%and MFI) expression in 2,3 and 4 group were higher than 1 group (10.96, 23.56, 23.60 vs 1.90 p<0.01. 36.2, 45.6, 45.6 vs 23.5 p<0.01). (4)The content of NO in plasma and platelets, the activity of NOS and production of cGMP were related positively one another. Exeept CD62p% did not correlate with plasma concentration of NO,CD62p (% or MFI ) and PAC-1 (%orMFI) were negatively related with the content of NO in plasma and platelets, the activity of NOS and production of cGMP one another. Conclusion (1)The decreasing of NO level in platelets correlated with lowering of NOS activity as well as L-arginine transport dysfunction in patients with hypertension. (2)The activity of NOS in platelets in patients with hypertension complicated with angina pectoris were decreased morethan those in patients with single hypertension, in this group the maxim transport velocity (Vmax) of L-3H arginine transport was not lowered compared with that in patients with single hypertension. So we concluded the decreasing of NO in patients with hypertension complicated with angina pectoris is resulted from more decreasing of the NOS activity in platelets. (3)The reduction of plasma NO and dysfunction of L-3H arginine transport were more serious in the patients with hypertension complicated with diabetes mellitus. (4)There was not difference of CD62p (% or MFI) between control group and single hypertension group. But There was a significant difference of PAC-1 (% or MFI) between this two groups. These suggested the PAC-1 may be a sensitive and specific molecular marker on the surface of activated platelets. There was platelet activation in older hypertensive patients. Even though the blood pressure was normal, the expression of markers was increased and function of L-arginine/No pathway was decreased.So it isimportant for us to give antihplatelet drugs and No donor besides antihypertensive drugs. (5)The expression of CD62 and PAC-1 in older patients with hypertension complicated with angina pectoris or diabetes mellitus were higher than control group and single...