Interactions among Endothelial Nitric Oxide Synthase, Cardiovascular System, and Nociception during Physiological and Pathophysiological States

Figures

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  Figure 1. Formation of nitric oxide (NO) from L-Arginine in the presence of co-factor tetrahydropbiopterin (BH4) and endothelial nitric oxide synthase (eNOS). The vascular endothelial cells produce NO by utilizing eNOS. The NO then diffuses from vascular endothelia to vascular smooth muscle cells. Inside the smooth muscles, NO activates guanylate cyclase, which converts GTP to cGMP. cGMP relaxes the vascular smooth muscle cells, resulting in vasodilation.

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  Figure 2. Mechanism of how initial tissue injury leads to pain reduction through activation of eNOS, production of nitric oxide (NO), and increase in cGMP. eNOS is stimulated in vascular endothelia by tissue injury, such as knee injury, skin laceration, and wounds. NO, which is produced by eNOS, diffuses to the vascular smooth muscle cells. Upon stimulation by NO, guanylate cyclase converts GTP to cGMP, resulting in vascular smooth muscle relaxation. Vasodilation has been shown to be associated with pain reduction, possibly through reduced inflammation and increased angiogenesis.

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  Figure 3. Average time-course changes in mean arterial pressure (MAP: upper panel) and heart rate (HR: lower panel) during 10 s hind paw mechanical stimuli 120 min after bilateral insertion of microdialysis probes into the dorsolateral periaqueductal gray matter (control: blue circles) and 30 min after microdialysis of L-N(5)-(1-iminoethyl) ornithine (L-NIO: 10 µM: red triangles; an endothelial nitric oxide synthase antagonist) into the same area of anesthetized rats. The Y-axes are changes in MAP or HR, and the yellow boxes represent the 10 s time of stimulation. Values represent means ± SEM (n = 8).

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  Figure 4. Average time-course changes in mean arterial pressure (MAP: upper panel) and heart rate (HR: lower panel) during 10 s hind paw heat-induced thermal stimuli 120 min after bilateral insertion of microdialysis probes into the dorsolateral periaqueductal gray matter (control: blue circles) and 30 min after microdialysis of L-N(5)-(1-iminoethyl)ornithine (L-NIO: 10 µM: red triangles; an endothelial nitric oxide synthase antagonist) into the same area of anesthetized rats. The Y-axes are changes in MAP or HR, and the yellow boxes represent the 10 s time of stimulation. Values represent means ± SEM (n = 8) and * p < 0.05 represents value versus control.

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  Figure 5. Average time-course changes in mean arterial pressure (MAP: upper panel) and heart rate (HR: lower panel) during 10 s hind paw immersion in a 10 °C cold-water bath 120 min after bilateral insertion of microdialysis probes into the periaqueductal gray matter (control: blue circles) and 30 min after microdialysis of L-N(5)-(1-iminoethyl)ornithine (L-NIO: 10 µM: red triangles; an endothelial nitric oxide synthase antagonist) into the dorsolateral periaqueductal gray matter of anesthetized rats. The Y-axes are changes in MAP or HR, and the yellow boxes represent the 10 s time of stimulation. Values represent means ± SEM (n = 8) and * p < 0.01 represents values versus control.