N-terminal chromogranin-derived peptides as dilators of bovine coronary resistance arteries

N-terminal peptides of chromogranin A and B (CGA and CGB) were compared for dilator responses in isolated bovine coronary arteries (bCoA), measuring diameter changes as a function of pressure. bCoA developed and maintained myogenic tone (MYT) at similar to20% from 50 to 150 mm Hg. In contrast to CGB(1-40), CGA(1-40) and CGA(1-76) (VS-I) both displayed significant intrinsic vasodilator effects. CGA(1-40) reduced myogenic reactivity from 70 to 150 mm Hg (p < 0.05, n = 6). At 75 mm Hg, CGA(1-40) showed a concentration-dependent dilatation at 0.1 nM-10 mu M The dilator effect of CGA(1-40) Persisted at moderately elevated [K+], (8.4-16 mM). However, this effect was diminished by pertussis toxin (PTX) and abolished by antagonists to several subtypes of K+ channels (tetraethylammonium, Ba2+ and glibenclamide). These results demonstrate that the N-terminal domain of CGA has dilator effect in the myogenically active bCoA. We propose that CGA(1-40) and the naturally occurring vasostatin I are regulatory peptides of relevance for the coronary microcirculation and that a G(alpha i) sub-unit and K+ channel activation may be involved in the signal pathway. (C) 2002 Elsevier Science B.V All rights reserved.