MODIFICATION OF MYOGENIC INTRINSIC TONE AND [CA2+]I OF RAT ISOLATED ARTERIOLES BY RYANODINE AND CYCLOPIAZONIC ACID

The role of the sarcoplasmic reticulum (SR) in regulating myogenic ton e and [Ca2+]i was examined with ryanodine and cyclopiazonic acid (CPA) in the rat skeletal muscle arteriole (A(sk)) and mesenteric arteriole (A(ms)). Arterioles were cannulated at both ends to control luminal p ressure in a tissue bath. Luminal diameter was measured with a video-m onitored microscopic system. Fura 2-AM was loaded to measure [Ca2+]i u sing the fluorescence intensity ratio at excitation wavelengths of 340 to 380 nm (F340/380). The myogenic response (luminal pressure was inc reased from 40 to 100 mm Hg) and the intrinsic tone at 40 mm Hg were o bserved in A(sk) but not in A(ms). Ryanodine (10(-5) M) decreased the steady-state diameter Of A(sk) from 138+/-8 to 85+/-9 mum (P<.05) and increased the F340/380 ratio; these effects were reversed by nifedipin e or Ca2+-free solution. Ryanodine shifted the [Ca2+]o-contraction res ponse curve upward. CPA (10(-5) M) also decreased the steady-state dia meter Of A(sk) from 131+/-7 to 98+/-11 mum (P<.05). In contrast, A(ms) responded to neither ryanodine nor CPA. Caffeine-induced contractions were significantly reduced by either ryanodine or CPA in both arterio les. These results indicate that SR dysfunction increased the suscepti bility of the arteriolar tone to [Ca2+]o and enhanced the tone Of A(sk ). In conclusion, the SR function may play a critical role in regulati ng [Ca2+]i and the intrinsic tone of A(sk) that was myogenically activ e at physiological luminal pressure.