Potassium channel opener's (KCOs) were originally thought of as nonselective smooth muscle relaxants. However, recent investigations in animal models of both
peripheral vascular disease (PVD) and
asthma have revealed interesting effects of these drugs as unexpectedly low doses. Hemodynamically, KCOs are interesting in PVD since they have little effect on blood supply to normally perfused skeletal muscle, but enhance perfusion to chronically ligated ischemic tissue. In animal PVD models,
SDZ PCO-400 and
cromakalim have been shown to improve recovery of muscle energy stores from
ischemia or to preserve performance under conditions of
ischemic contracture. Beneficial effects in rat PVD models were manifest at doses below those affecting systemic blood pressure and may be attributable to a selective dilatation of collateral vessels. With regard to the airways, the apparent efficacy of KCOs as
antiasthmatic drugs seems not to be attributable solely to their
bronchodilator activity. Although KCOs elicit no antiinflammatory effect in animal models, studies with
SDZ PCO-400 in guinea pigs sensitized to
antigen or treated with
immune complexes have revealed that expression of airway hyperreactivity is significantly inhibited at
drug doses exhibiting only modest
bronchodilator activity. At least part of this action can be attributed to inhibition at the level of neural innervation of the airways, possibly through attenuation of nonadrenergic noncholinergic (NANC) transmission.(ABSTRACT TRUNCATED AT 250 WORDS)