pituitrin and tetramethylammonium

Rat renal interlobar arteries express heme oxygenase 2 (HO-2) and manufacture carbon monoxide (CO), which is released into the headspace gas. CO release falls to 30% and 54% of control, respectively, after inhibition of HO activity with chromium mesoporphyrin (CrMP) or of HO-2 expression with antisense oligodeoxynucleotides (HO-2 AS-ODN). Patch-clamp studies revealed that CrMP decreases the open probability of a tetraethylammonium-sensitive (TEA-sensitive) 105 pS K channel in interlobar artery smooth muscle cells, and that this effect of CrMP is reversed by CO. Assessment of phenylephrine-induced tension development revealed reduction of the EC(50) in vessels treated with HO-2 AS-ODN, CrMP, or TEA. Exogenous CO greatly minimized the sensitizing effect on agonist-induced contractions of agents that decrease vascular CO production, but not the sensitizing effect of K channel blockade with TEA. Collectively, these data suggest that vascular CO serves as an inhibitory modulator of vascular reactivity to vasoconstrictors via a mechanism that involves a TEA-sensitive K channel.

Topics: Animals; Arteries; Carbon Monoxide; Dose-Response Relationship, Drug; Drug Antagonism; Heme Oxygenase (Decyclizing); Kidney; Male; Mesoporphyrins; Muscle, Smooth, Vascular; Patch-Clamp Techniques; Phenylephrine; Potassium Channels; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley; Up-Regulation; Vasoconstrictor Agents; Vasopressins