Membrane stretch evoked by cell swelling increases contractile activity in vascular smooth muscle through dihydropyridine-sensitive pathways.
Effects of the dihydropyridine calcium antagonist felodipine and of calcium reduction were studied on osmotically induced contractile responses in the vascular smooth muscle of the rat isolated portal vein. Previous studies have shown that changes in osmolarity that cause cell swelling are accompanied by increased contractile activity in this smooth muscle (Johansson & Jonsson 1968). A transient enhancement of the contractile activity developed in the portal vein on return to standard Krebs solution after exposure to 60 mM urea. This osmotic response was dependent on extracellular Ca2+ (abolished in Ca2+ free solution +0.1 mM EGTA) and was reduced in proportion to the decrease in spontaneous phasic contractile activity when Ca2+ was lowered from the standard 2.5 mM concentration. Felodipine, 3 nM, reduced the spontaneous activity to approximately 50% but showed an even more pronounced inhibitory effect on the osmotic responses which were reduced to less than 20% of control. Other calcium antagonists such as verapamil, 60 nM and diltiazem, 300 nM, were also more effective in inhibiting the osmotic responses than the spontaneous activity. In contrast, the K+ channel opener, pinacidil, 100-200 nM, reduced the spontaneous activity to 50% but had only minor inhibitory effect on the osmotic responses, about 75% still persisting. It is suggested that stretch of the cell membrane in response to variations in osmolarity induces contractile activity in vascular smooth muscle by mechano-electrical coupling involving dihydropyridine-sensitive pathways.
Bülow
A
A
Department of Physiology, University of Göteborg, Sweden.
Johansson
B
B
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D048429:Cell Size / Q000502:physiology*; D004095:Dihydropyridines / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D015736:Felodipine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009995:Osmosis / Q000187:drug effects; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D014700:Verapamil; D004110:Diltiazem; D015736:Felodipine; D002118:Calcium