Low K+ current in arterial myocytes with impaired K+-vasodilation and its recovery by exercise in hypertensive rats

Abstract

K(+) channels determine the plasma membrane potential of vascular myocytes, influencing arterial tone. In many types of arteries, a moderate increase in [K(+)]e induces vasorelaxation by augmenting the inwardly rectifying K(+) channel current (I Kir). K(+)-vasodilation matches regional tissue activity and O2 supply. In chronic hypertension (HT), small arteries and arterioles undergo various changes; however, ion channel remodeling is poorly understood. Here, we investigated whether K(+) channels and K(+)-induced vasodilation are affected in deep femoral (DFA) and cerebral artery (CA) myocytes of angiotensin II-induced hypertensive rats (Ang-HT). Additionally, we tested whether regular exercise training (ET) restores HT-associated changes in K(+) channel activity. In Ang-HT, both the voltage-gated K(+) channel current (I Kv) and I Kir were decreased in DFA and CA myocytes, and were effectively restored and further increased by combined ET for 2 weeks (HT-ET). Consistently, K(+)-vasodilation of the DFA was impaired in Ang-HT, and recovered in HT-ET. Interestingly, ET did not reverse the decreased K(+)-vasodilation of CA. CA myocytes from the Ang-HT and HT-ET groups demonstrated, apart from K(+) channel changes, an increase in nonselective cationic current (I NSC). In contrast, DFA myocytes exhibited decreased I NSC in both the Ang-HT and HT-ET groups. Taken together, the decreased K(+) conductance in Ang-HT rats and its recovery by ET suggest increased peripheral arterial resistance in HT and the anti-hypertensive effects of ET, respectively. In addition, the common upregulation of I NSC in the CA in the Ang-HT and HT-ET groups might imply a protective adaptation preventing excessive cerebral blood flow under HT and strenuous exercise.

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

“…In rats, angiotensin II-induced hypertension reduces SMC K IR channel current density and K + -induced dilation of skeletal muscle and cerebral arteries (1281). In the skeletal muscle artery SMCs, 2 weeks of exercise training reversed the effects of hypertension on K IR channel currents and K + -induced dilation (1281).…”

“…In the skeletal muscle artery SMCs, 2 weeks of exercise training reversed the effects of hypertension on K IR channel currents and K + -induced dilation (1281). While K IR channel currents were restored by exercise in cerebrovascular myocytes, K + -induced dilation remained depressed (1281) suggesting regional heterogeneity in the response to exercise training. Previous studies showed that exercise training augments expression and function of vascular SMC K IR channels (709).…”

Exercise and Ion-Channel Remodeling in Vascular Smooth Muscle During Hypertension: Therapeutic Implications

“…The changes in Kir channels during hypertension are currently inconclusive. Previous studies have shown a reduced function of Kir channels during hypertension [61], which complements the compensatory upregulation of the neuronal nitric oxide synthase (nNOS) pathway [11] and an increase in nonselective cationic current [61] to reduce organ blood flow. However, other studies have demonstrated that upregulation of Kir channels in cerebral microvessels acts as an adaptive mechanism to preserve cerebral blood flow during chronic hypertension [53].…”

Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth

“…The effects of hypertension on K IR channel function are not clear; increases (Nakahata et al, 2006), decreases (Seo et al, 2014), or no change in function (Tajada et al, 2012) have been reported. Similarly, diabetes has been reported to increase (Troncoso Brindeiro et al, 2008; Troncoso Brindeiro, Lane, & Carmines, 2012) or decrease (Matsushita & Puro, 2006; Mayhan, Mayhan, Sun, & Patel, 2004; Vetri et al, 2012) K IR channel function in different models.…”