The impact on blood pressure of two vasodilating mechanisms, underlied by vascular smooth muscle hyperpolarization, was studied and compared to that induced by nitric oxide (NO) mechanism. Systemic blood pressure, after inhibitory intervention in arachidonic acid metabolism (cytochrome P-450 inhibition by miconazole 0.5 mg/100 g b.w.), one of the hyperpolarizing pathways, did not change. After the inhibition of the action voltage-dependent K+ channels operator (by 4-aminopyridine 0.1 mg/100 g b.w.)
, the other hyperpolarizing pathway, blood pressure declined slightly (from 132.3±3.2 mm Hg to 116.5±5.0 mm Hg, P<0.05). Inhibition of nitric oxide production (L-NAME 5 mg/100 g b.w.) increased blood pressure considerably (123.5±2.7 mm Hg to 155.4±3.1 mm Hg, P<0.001). After inhibition of the hyperpolarizing pathway by miconazole, hypotension induced by acetylcholine (Ach, 10 μg) represented 63.0±1.9 mm Hg vs control value 78.6±5.2 mm Hg (P<0.001), by bradykinin (BK) (100 μg) 59.4±3.9 mm Hg vs control value 71.2±6.1 mm Hg (P<0.05). After inhibition of the hyperpolarizing pathway by 4-aminopyridine, hypotension induced by ACh (10 μg) achieved 64.6±2.5 mm Hg vs control value 78.4±2.8 mm Hg (P<0.001) and that induced by BK (100 μg)
56.6±5.3 mm Hg vs control value 72.3±2.5 mm Hg (P<0.001). ACh or BK hypotension after the inhibition of the above hyperpolarizing pathways was significantly attenuated. On the contrary, after NO-synthase inhibition the hypotension to ACh was significantly enhanced. Blood pressure decrease after ACh (10 μg) hypotension was 91.8±4.1 mm Hg vs control value 79.3±3.3 mm Hg (P<0.01), and after BK (100 μg) it was 78.4±7.1 mm Hg vs control value 68.3±5.2 mm Hg. A different basal BP response, but equally attenuated hypotension to Ach and BK, was detected after the inhibition of two selected hyperpolarizing pathways. In cotrast, the inhibition of NO production elicited an increase in systemic BP and augmentation of ACh and BK hypotension. The effectiveness of further hyperpolarizing mechanisms in relation to systemic BP regulation and nitric oxide level remains open.