Endothelin‐1 increases the frequency of smooth muscle calcium waves in vena cava but not aorta

Abstract

Vascular contraction is associated with a global increase in smooth muscle Ca2+. The frequency and amplitude of localized intracellular Ca2+ release events, such as IP3 receptor‐mediated Ca2+ waves, can also regulate excitation‐contraction coupling in smooth muscle. While the vasoconstrictor ET‐1 does increase IP3 formation, it is unclear if IP3 receptor‐mediated Ca2+ waves are a regulator of ET‐1‐induced contraction in arteries and veins. We hypothesized that ET‐1 increases the frequency and amplitude of Ca2+ waves in rat aorta (RA) and vena cava (RVC). RA and RVC were mounted en face in an imaging superfusion chamber and incubated with the intensiometric fluorescent Ca2+ indicator Fluo 4‐AM (10 μM). Using spinning‐disc confocal microscopy, image sequences were first recorded with buffer alone, and then maximal contractile concentrations of norepinephrine (NE, 10 μM) (RVC) or phenylephrine (PE, 10 μM) (RA), and finally ET‐1 (100 nM). ET‐1 (100 nM) increased Ca2+ wave frequency significantly in RVC versus control (0.72±0.16 Hz vs. 0.45±0.13 Hz), but not in RA. Neither NE (10 μM) nor PE (10 μM) altered Ca2+ wave frequency or amplitude in RA and RVC. These data indicate that intracellular Ca2+ mobilization by ET‐1 is different in arteries and veins. These data also provide indirect evidence that ET receptors are coupled to IP3‐mediated Ca2+ release mechanisms in the vena cava but not aorta. Supported by NIH P01HL70687.