Reduction in extracellular Ca2+ attenuates endothelium-dependent relaxation more than nitroprusside-induced relaxation.
OBJECTIVE
To quantitatively assess the effect of lowering external Ca(2+) ([Ca(2+)](o)) on both endothelium-dependent and -independent relaxations in rabbit aorta.


METHODS
Isometric contractions and relaxations of isolated aortae were recorded. When assessing the effect of reduced [Ca(2+)](o) on relaxations, the normal [Ca(2+)](o) solution was substituted with one of the reduced [Ca(2+)](o) solutions for one aorta, while a paired aorta was replenished with normal [Ca(2+)](o) solution.


RESULTS
The extent of acetylcholine (ACh)-induced relaxation, which is dependent on an intact endothelium, is time-dependent, and inversely related to [Ca(2+)](o) in a range of 0.02-2 mmol/L. ACh-induced relaxations were not significantly altered by the magnitude of the precontraction induced by PGF(2alpha). Nitroprusside-induced relaxations, which are independent of the endothelium, are also attenuated by reduced [Ca(2+)](o). Relaxant responses to ACh were significantly more susceptible to reduced [Ca(2+)](o) than nitroprusside-induced relaxations. A maximally effective relaxing concentration of D600, an L-type Ca channel blocker methoxyverapamil, (10(-5) mol/L) attenuated ACh-induced relaxations, whereas nitroprusside-induced relaxations were unaffected by D600.


CONCLUSIONS
Thus, endothelium-dependent relaxation is more dependent on [Ca(2+)](o) than endothelium-independent relaxation, and it seems likely that [Ca(2+)](o) plays an important role not only in contractile processes, but also in relaxant processes as well.
Hayashi
Shigehiro
S
Department of Medical Pharmacology and Toxicology, and Microcirculation Research Institute, College of Medicine, Texas A&M University, College Station, TX 77843-1114, USA. s-hayashi@pha.ohu-u.ac.jp
Hester
R Kelly
RK
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D014665:Vasodilator Agents; D009599:Nitroprusside; D005711:Gallopamil; D015237:Dinoprost; D000109:Acetylcholine; D002118:Calcium