Abstract
The exposure of helically cut strips of aorta of spontaneously hypertensive rats (SHR) and Wistar Kyoto normotensive control strain rats (WKY) to 6(N, N-diethylamino)hexyl 3,4,5-trimethoxybenzoate (TMB-6) blocked norepinephrine (NE, 0.08–0.4 μM) induced contractions. The tension developed in the SHR aorta was lower than that developed in the aorta of WKY rats at equal doses of NE. All doses of TMB-6 decreased responses to low and high levels of NE, indicating a noncompetitive antagonism. The ED50 value with TMB-6 WKY rat aorta was 110 μM and for SHR aorta was 38 μM. Microsomal calcium uptake in rat aorta reflected sarcoplasmic reticulum calcium sequestration. A calcium uptake of 70 nmol/mg protein/60 min was observed with WKY rat aorta microsomes. Calcium uptake of 50 nmol/mg protein/60 min was observed with microsomes prepared from SHR rat aorta. TMB-6 (1 mill) depressed the microsomal calcium uptake in 60 min by only 15% and had no effect on the release of calcium from the preloaded microsomes. The increased sensitivity of SHR aorta to TMB-6 was compatible with a decreased internal calcium store in the SHR aorta reflected in the decreased calcium uptake of the sarcoplasmic reticulum and an increased dependency on influx of external medium calcium blocked by TBM-6. The experimental findings did not indicate a significant effect by TMB-6 on sarcoplasmic reticulum calcium uptake or release. TMB-6 may interfere with the inflow of medium calcium into the smooth muscle cells which is utilized for contraction or may also interfere with the signal to the sarcoplasmic reticulum for release of calcium.