Systemic and regional hemodynamic responses to tempol in angiotensin II-infused hypertensive rats

Recent studies have indicated that angiotensin II (Ang Il) can stimulate ox idative stress. The present study was conducted to assess the contribution of oxygen radicals to hypertension and regional circulation during Ang II-i nduced hypertension. With radioactive microspheres, the responses of system ic and regional hemodynamics to the membrane-permeable, metal-independent s uperoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (te mpol) were assessed in conscious Ang II-infused hypertensive rats. Ang II-i nfused rats (80 ng/min SC for 12 days: n=25) showed higher mean arterial pr essure (MAP: 161+/-4 mm Hg) and total peripheral resistance (TPR: 1.59+/-0. 08 mm Hg min(-1) . mL(-1)) than vehicle-infused normotensive rats (116+/-3 mmHg and 0.95+/-0.04 mmHg . min(-1) . mL(-1), respectively; n=23). The bloo d flow rates in the brain, spleen, large intestine, and skin were significa ntly reduced in Ang II-infused rats compared with vehicle-infused rats, whe reas rates in the lung, heart, liver, kidney, stomach, small intestine, mes enterium, skeletal muscle, and testis were similar. Vascular resistance was significantly increased in every organ studied except the lung, in which t he resistance was similar. Tempol (216 mu mol/kg IV) significantly reduced MAP by 30+/-4% from 158+/-7 to 114+/-5 mm Hg and TPR by 35+/-6% from 1.57+/ -0.17 to 0.95+/-0.04 mm Hg . min(-1) . g(-1) in Ang II-infused rats (n=9) b ut had no effect on these parameters in vehicle-infused rats (n=8). In Ang II-infused rats, tempol did not affect regional blood flow but significantl y decreased vascular resistance in the brain (29+/-6%), heart (31+/-6%), li ver (37+/-7%), kidney (30+/-7%), small intestine (38+/-6%), and large intes tine (47+/-7%). Ang II-infused hypertensive rats showed doubled vascular su peroxide production (assessed with lucigenin chemiluminescence), which was normalized by treatment with tempol (3 mmoI/L, n=7). Further studies showed that the NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (II mu mol . kg(-1) . min(-1) IV, n=11) markedly attenuated the systemic and re gional hemodynamic responses of tempol in Ang II-infused rats. These result s suggest that in this model of hypertension, oxidative stress may have con tributed to the alterations in systemic blood pressure and regional vascula r resistance through inactivation of NO.