Influence of hypertension on cardiac contractile response of human erythrocyte-derived depressing factor in ventricular myocytes.
BACKGROUND
Erythrocyte-derived depressing factor (EDDF), a novel hypotensive factor purified from human erythrocytes, elicits endothelium-dependent vasorelaxation by reducing intracellular Ca2+ in vascular smooth muscle cells. However, its cardiac response is unknown.


OBJECTIVE
This study was designed to examine the cardiac contractile response of EDDF under both normotensive and hypertensive conditions.


METHODS
Ventricular myocytes were isolated from adult male spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) normotensive rats. Mechanical properties were evaluated using an IonOptix MyoCam system and intracellular Ca2+ was measured with fura-2 fluorescence. Myocytes were electrically stimulated to contract at 0.5 Hz. The contractile properties analyzed included peak shortening (PS), time-to-PS (TPS), time-to-90% re-lengthening (TR(90)), maximal velocity of shortening/re-lengthening (+/- dl/dt), fura-fluorescence intensity change (DeltaFFI), and fura-fluorescence decay rate (tau).


RESULTS
SHR rats displayed significantly elevated blood pressure. EDDF (10-9-10-4 g/ml) did not affect PS, TPS, TR(90), DeltaFFI and tau but depressed +/- dl/dt at higher doses in WKY myocytes. However, EDDF depressed PS, +/- dl/dt and DeltaFFI, shortened TPS without affecting TR(90) and tau in SHR myocytes. Pretreatment of the myocytes with the nitric oxide synthase inhibitor Nvarpi-nitro-l-arginine methyl ester (l-NAME) did not affect the EDDF-induced inhibition of PS and +/- dl/dt in SHR myocytes but unmasked an EDDF-induced negative response in WKY myocytes.


CONCLUSIONS
These data indicate that EDDF may participate in the modulation of cardiac contractile function under hypertensive, but not normotensive, conditions. The cardiac depressive effect of EDDF is unlikely due to release of nitric oxide, as suggested in vascular smooth muscles.
Ren
Jun
J
Division of Pharmaceutical Sciences, University of Wyoming College of Health Sciences, Laramie, Wyoming 82071-3375, USA. jren@uwyo.edu
Wen
Yunyi
Y
Hintz
Kadon K
KK
D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D001685:Biological Factors; D004791:Enzyme Inhibitors; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester