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 chronic diabetic rats. Twelve weeks after streptozotocin (STZ) injection, the systolic blood pressures (SBP) of diabetic groups have been found to be significantly 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 enhanced in diabetic rats compared with control subjects. Treatment of diabetic rats with L-ARG completely reversed the increases in responsiveness and sensitivity of aortae to PE. The relaxation response to acetylcholine (ACh), but not to sodium nitroprusside (SNP), in diabetic aorta has been found to be significantly decreased when compared with control subjects. The in vivo treatment with L-ARG reversed the decreased ACh responses to the control level. Plasma malondialdehyde (MDA) level of diabetic rats was also significantly 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-ARG treatment were found to be specific for diabetic rats but not control subjects. These results show that L-ARG treatment in vivo has a reversal effect on impaired vascular responses and increased oxidative stress. The present findings also suggest that oxidative stress that occurred in diabetes might cause or contribute to the development of hypertension by affecting vascular reactivity. On the other hand, the lipid peroxidation-lowering effect of L-ARG may account for its beneficial effect on SBP and vascular responsiveness of diabetic rats.
Ozçelikay
A T
AT
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, 06100, Turkey.
Tay
A
A
Güner
S
S
Taşyaran
V
V
Yildizoğlu-Ari
N
N
Dinçer
U D
UD
Altan
V M
VM
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D001808:Blood Vessels / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001786:Blood Glucose; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D008315:Malondialdehyde; D001120:Arginine