Reversal effects of L-arginine treatment on blood pressure and vascular responsiveness of streptozotocin-diabetic rats

In the present study, we examined the reversal effects of L-arginine (L-ARG ) treatment in vivo on blood pressure and on vascular responsiveness of chr onic diabetic rats. Twelve weeks after streptozotocin (STZ) injection, the systolic blood pressures (SBP) of diabetic groups have been found to be sig nificantly higher compared with that of control groups. L-ARG treatment for 4 weeks, begun 12 weeks after the onset of diabetes, induced a significant fall in SBP of diabetic rats. Maximal contractile response and sensitivity (pD(2) value) of the aortae to phenylephrine (PE) were significantly enhan ced in diabetic rats compared with control subjects. Treatment of diabetic rats with L-ARG completely reversed the increases in responsiveness and sen sitivity of aortae to PE. The relaxation response to acetylcholine (ACh), b ut not to sodium nitroprusside (SNP), in diabetic aorta has been found to b e significantly decreased when compared with control subjects. The in vivo treatment with L-ARG reversed the decreased ACh responses to the control le vel. Plasma malondialdehyde (MDA) level of diabetic rats was also significa ntly higher than control subjects. However, L-ARG treatment normalized the increase in MDA level of plasma of diabetic rats. All of the effects of L-A RG treatment were found to be specific for diabetic rats but not control su bjects. These results show that L-ARG treatment in vivo has a reversal effe ct on impaired vascular responses and increased oxidative stress. The prese nt findings also suggest that oxidative stress that occurred in diabetes mi ght cause or contribute to the development of hypertension by affecting vas cular reactivity. On the other hand, the lipid peroxidation-lowering effect of L-ARG map account for its beneficial effect on SBP and vascular respons iveness of diabetic rats. (C) 2000 Academic Press.