Mortal hyperkalemia disturbances in rats are NO-system related. The life saving effect of pentadecapeptide BPC 157

Abstract We demonstrate the full counteracting ability of stable gastric pentadecapeptide BPC 157 against KCl-overdose (intraperitoneal (i), intragastric (ii), in vitro (iii)), NO-system related. (i) We demonstrated potential (/kg) of: BPC 157 (10 ng, 10 μg ip, complete counteraction), l -arginine (100 mg ip, attenuation) vs. L-NAME (5 mg ip, deadly aggravation), given alone and/or combined, before or after intraperitoneal KCl-solution application (9 mEq/kg). Therapy was confronted with promptly unrelenting hyperkalemia (> 12 mmol/L), arrhythmias (and muscular weakness, hypertension, low pressure in lower esophageal and pyloric sphincter) with an ultimate and a regularly inevitable lethal outcome within 30 min. Previously, we established BPC 157-NO-system interaction; now, a huge life-saving potential. Given 30 min before KCl, all BPC 157 regimens regained sinus rhythm, had less prolongation of QRS, and had no asystolic pause. BPC 157 therapy, given 10 min after KCl-application, starts the rescue within 5–10 min, completely restoring normal sinus rhythm at 1 h. Likewise, other hyperkalemia-disturbances (muscular weakness, hypertension, low sphincteric pressure) were also counteracted. Accordingly with NO-system relation, deadly aggravation by L-NAME: l -arginine brings the values to the control levels while BPC 157 always completely nullified lesions, markedly below those of controls. Combined with l -arginine, BPC 157 exhibited no additive effect. (ii) Intragastric KCl-solution application (27 mEq/kg) — (hyperkalemia 7 mmol/L): severe stomach mucosal lesions, sphincter failure and peaked T waves were fully counteracted by intragastric BPC 157 (10 ng, 10 μg) application, given 30 min before or 10 min after KCl. (iii). In HEK293 cells, hyperkalemic conditions (18.6 mM potassium concentrations), BPC 157 directly affects potassium conductance, counteracting the effect on membrane potential and depolarizations caused by hyperkalemic conditions.