Background: Regular exercise is an effective non-pharmacological therapy for prevention and control of hypertension. However, the underlying molecular mechanisms remain unresolved. We
tested the hypothesis that hypertension would increase the functional coupling of large-conductance Ca2+-activated K+ (BKCa) channels with ryanodine receptors (RyRs) in spontaneously hypertensive rats
(SHR) as a compensatory response to an increase in intracellular Ca2+ concentration in cerebral arterial smooth muscle cells (CASMCs). We also hypothesized that exercise training would prevent this
increase in functional coupling.
Methods: Male SHRs and Wistar-Kyoto rats (WKYs), 12 weeks age, were separated into sedentary groups (SHR-SED and WKY-SED) and exercise groups (SHR-EX and WKY-EX) at random. Rats in
exercise group were subjected to a treadmill training protocol: 18~20 m/min (about 55-65% of maximal aerobic velocity), 0% grade, 60 min/d, 5 d/wk for 8 weeks.
Results: Cerebral myocytes displayed spontaneous transient outward currents (STOCs) at membrane potentials more positive than -40 mV. STOC amplitude in SHR-SED was higher than that in
WKY-SED at the same holding potential. The amplitude of the spontaneous Ca2+ sparks in isolated CASMCs was significantly enhanced in SHRs. Moreover, hypertension displayed increased whole-cell BKCa,
Cav1.2 but decreased KV currents in CASMCs. The single BKCa channel activity was markedly enhanced, and protein expression of BKCa (β1, but not α-subunit) was significantly increased but KV1.2 was
decreased in SHRs. Exercise training ameliorated all of these functional and molecular alterations in hypertensive rats.
Conclusions: These data indicate that hypertension leads to an enhanced functional coupling of RyRs-BKCa to buffer pressure-induced constriction of cerebral arteries, which attributes
not only to an upregulation of BKCa β1-subunit function but also to an increase of Ca2+ release from RyRs. However, regular aerobic exercise can efficiently prevent the augmented coupling to alleviate
the pathological compensation to restore the cerebral arterial function.