Myofilament Calcium Sensitivity of Normotensive and Hypertensive Resistance Arteries

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Abstract
Abstract We measured intracellular Ca 2+ and isometric force simultaneously in endothelium-denuded mesenteric resistance arteries of 12- to 15-week-old male spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, and Wistar rats. Basal Ca 2+ did not differ among vessels of these strains (SHR, 86.6±4.5 nmol/L; WKY, 78.5±4.7 nmol/L; Wistar, 83.1±3.9 nmol/L). Myofilament Ca 2+ sensitivity was determined by measuring the intracellular Ca 2+ and force responses to cumulative addition of extracellular Ca 2+ (0.025 to 2.5 mmol/L) in the presence of 100 mmol/L K + or 10 μmol/L norepinephrine after depletion of releasable intracellular Ca 2+ stores. With 100 mmol/L K + , no between-strain differences in active stress, intracellular Ca 2+ , or myofilament Ca 2+ sensitivity were observed. With 10 μmol/L norepinephrine, the active stress response of SHR vessels to 0.025 and 0.05 mmol/L Ca 2+ was increased compared with both normotensive strains. The intracellular Ca 2+ response was not different in vessels of SHR and WKY rats but was depressed in Wistar vessels. Myofilament Ca 2+ sensitivity of SHR was elevated compared with both WKY and Wistar rats ( P <.05) (ED 25 for SHR, 74.4±5.1 nmol/L; WKY, 89.8±5.5 nmol/L; Wistar, 86.9±3.4 nmol/L). No strain differences in intracellular Ca 2+ or active stress responses of SHR and WKY vessels were detected during cumulative addition of norepinephrine with constant extracellular Ca 2+ (1.5 mmol/L). These results indicate that no hypertension-associated defect in vascular Ca 2+ handling exists in mesenteric arteries of the SHR. Moreover, although resistance arteries of SHR exhibit enhanced myofilament Ca 2+ sensitivity compared with two normotensive strains after depletion of intracellular Ca 2+ and activation with 10 μmol/L norepinephrine, this difference is not observed under the more physiological manipulation of cumulative addition of norepinephrine in the presence of constant Ca 2+ . We conclude that enhanced myofilament Ca 2+ sensitivity is unlikely to contribute to the hypertension of SHR.