Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells?

Specialized O2-sensing cells exhibit a particularly low threshold to regulation by O2 supply and function to maintain arterial pO2 within physiological limits. For example, hypoxic pulmonary vasoconstriction optimizes ventilation-perfusion matching in the lung, whereas carotid body excitation elicits corrective cardio-respiratory reflexes. It is generally accepted that relatively mild hypoxia inhibits mitochondrial oxidative phosphorylation in O2-sensing cells, thereby mediating, in part, cell activation.

Comparative efficacies and durations of action of phenoxybenzamine, verapamil/nitroglycerin solution, and papaverine as topical antispasmodics for radial artery coronary bypass grafting.

Objective: Radial arteries are increasingly used as conduits for coronary artery bypass grafts, but perioperative graft vasospasm continues to be a concern. Phenoxybenzamine, verapamil/nitroglycerin solution, and papaverine have been advocated as topical antispasmodic agents. We compared the relative efficacies and durations of action of these agents.

Vasodilation by the calcium-mobilizing messenger cyclic ADP-ribose.

In artery smooth muscle, adenylyl cyclase-coupled receptors such as beta-adrenoceptors evoke Ca(2+) signals, which open Ca(2+)-activated potassium (BK(Ca)) channels in the plasma membrane. Thus, blood pressure may be lowered, in part, through vasodilation due to membrane hyperpolarization. The Ca(2+) signal is evoked via ryanodine receptors (RyRs) in sarcoplasmic reticulum proximal to the plasma membrane.

Hypoxic pulmonary vasoconstriction: cyclic adenosine diphosphate-ribose, smooth muscle Ca(2+) stores and the endothelium.

Hypoxic pulmonary vasoconstriction (HPV) is unique to pulmonary arteries, and supports ventilation/perfusion matching. However, in diseases such as emphysema, HPV can promote hypoxic pulmonary hypertension (HPH), which ultimately leads to right heart failure. Since it was first described, the mechanisms underpinning HPV have remained obscure, and current therapies for HPH are poor.