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 approximately 20% 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 microM. The dilator effect of CGA(1-40) persisted at moderately elevated [K(+)](e) (8.4-16 mM). However, this effect was diminished by pertussis toxin (PTX) and abolished by antagonists to several subtypes of K(+) channels (tetraethylammonium, Ba(2+) 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(alphai) sub-unit and K(+) channel activation may be involved in the signal pathway.
Brekke
Johan F
JF
Department of Physiology, University of Bergen, Arstadveien 19, 5009, Bergen, Norway.
Osol
George J
GJ
Helle
Karen B
KB
D000109:Acetylcholine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D037282:Calreticulin; D002417:Cattle; D053379:Chromogranin A; D053378:Chromogranin B; D002864:Chromogranins / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012261:Ribonucleoproteins / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D037282:Calreticulin; D053379:Chromogranin A; D053378:Chromogranin B; D002864:Chromogranins; D010446:Peptide Fragments; D010455:Peptides; D026902:Potassium Channel Blockers; D012261:Ribonucleoproteins; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; C067131:chromogranin A (1-40); C461742:chromogranin B (1-40); C121986:vasostatin; C064110:vasostatin I; D037342:Pertussis Toxin; D000109:Acetylcholine; D002118:Calcium