Protective Effect of Dietary Potassium Against Vascular Injury in Salt-Sensitive Hypertension

Abstract

Abstract-Hypertensive cardiovascular damage is accelerated by salt loading but counteracted by dietary potassium supplementation. We suggested recently that antioxidant actions of potassium contribute to protection against salt-induced cardiac dysfunction. Therefore, we examined whether potassium supplementation ameliorated cuff-induced vascular injury in salt-sensitive hypertension via suppression of oxidative stress. Four-week-old Dahl salt-sensitive rats were fed a normal-salt (0.3% NaCl), high-salt (8% NaCl), or high-salt plus high-potassium (8% KCl) diet for 5 weeks, and some of the rats fed a high-salt diet were also given antioxidants. One week after the start of the treatments, a silicone cuff was implanted around the femoral artery. Examination revealed increased cuff-induced neointimal proliferation with adventitial macrophage infiltration in arteries from salt-loaded Dahl salt-sensitive rats compared with that in arteries from non-salt-loaded animals (intima/media ratio: 0.471Ϯ0.070 versus 0.302Ϯ0.037; PϽ0.05), associated with regional superoxide overproduction and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and mRNA overexpression. On the other hand, simultaneous potassium supplementation attenuated salt-induced neointimal hyperplasia (intima/media ratio: 0.205Ϯ0.012; PϽ0.001), adventitial macrophage infiltration, superoxide overproduction, and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and overexpression. Antioxidants, which decrease vascular oxidative stress, also reduced neointima formation induced by salt excess. In conclusion, high-potassium diets seems to have a protective effect against the development of vascular damage induced by salt loading mediated, at least in part, through suppression of the production of reactive oxygen species probably generated by reduced nicotinamide-adenine dinucleotide phosphate oxidase. Key Words: hypertension Ⅲ sodium Ⅲ potassium Ⅲ antioxidants Ⅲ arteries N umerous studies have demonstrated that excessive salt intake causes cardiovascular damage and that this was counteracted by potassium supplementation. 1 According to the earlier report, 2 salt loading reduced the survival rate of Dahl salt-sensitive (DS) rats, a model of salt-sensitive hypertension, whereas potassium supplementation alleviated this salt-induced premature mortality, independent of its hypotensive action. It has been speculated that this may be a result of the vasoprotective effect of potassium, because potassium supplementation has been shown to ameliorate vascular endothelial dysfunction in salt-loaded DS rats. 3 Also, Ma et al 4 clearly demonstrated that high-potassium intake inhibited neointimal formation in several vascular injury models, such as a balloon injury of rat carotid and swine coronary 5 arteries from animals without hypertension. Thus, dietary potassium may have vasoprotective mechanisms beyond the blood pressure (BP)-lowering effect. Although it has been shown in in vitro experiments that potassium inhibited migration 6 an...

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“…6,[20][21][22][23][24] Second, hyperkalemia may occur less frequently in patients with a high salt diet than a low salt diet, because salt loading decreases serum K level. 33 Moreover, animal studies, including our own, 34,35 suggest that a mild increase in serum K level may promote organ protection in relatively K-depleted CKD patients with a high salt intake.…”

Inhibition of ROMK channels by low extracellular K+ and oxidative stress

“…Superoxide concentrations in renal cortex and outer medulla (2), as well as in vascular tissue (44), are increased with chronic K-restriction. Conversely, a high-K diet reduced ROS production in vascular tissue and protected against deleterious effects of a high Na intake (17). These effects may be mediated in part by angiotensin II (ANG II).…”

Potassium restores vasorelaxation of resistance arterioles in non-hypertensive DOCA/salt fed mice

“…The renal and cardiovascular protector effects of a potassiumenriched diet have been described in large epidemiological studies (Ascherio et al, 1992;Khaw and Barrett-Connor, 1987;Tobian, 1988), as well as in diverse animal models (Ellis et al, 1992;Jin et al, 1999;Kido et al, 2008;Wang et al, 2005), which have demonstrated that dietary potassium supplementation prevented vascular and renal injury caused by high salt intake. In this cardiovascular protector context, a pivotal role has been assigned to the anti-hypertensive effects of potassium, as well as to other vasoprotective mechanisms, such as the reduced production of reactive oxygen species (Matsui et al, 2006) and the direct inhibition of intimal hyperplasia (Kido et al, 2008).…”

“…In this cardiovascular protector context, a pivotal role has been assigned to the anti-hypertensive effects of potassium, as well as to other vasoprotective mechanisms, such as the reduced production of reactive oxygen species (Matsui et al, 2006) and the direct inhibition of intimal hyperplasia (Kido et al, 2008). Several authors have described a beneficial effect of potassium on the generation and release of nitric oxide (NO; see Zhou et al, 1999;Zhou et al, 2000) and a restoration of endothelium-dependent vasorelaxation has been shown in diverse hypertensive rat models (Sudhir et al, 1993;Sugimoto et al, 1988;Zhou et al, 1999).…”