Effects of oral calcium and potassium on endothelium-dependent relaxation in hypertensive rats

Abstract

High oral potassium (K) decreases stroke incidence in aging high salt-fed stroke-prone spontaneously hypertensive rats (SHRSP). We have seen high oral Ca increase stroke incidence in aging high salt-fed SHRSP without increasing blood pressure (BP) but with signs of K wasting. Therefore, we sought to determine whether high oral Ca suppresses the previously reported oral K-related enhancement of arterial endothelium-dependent relaxation as seen in younger high salt-fed SHRSP before the appearance of strokes. Four groups of female SHRSP were fed high-salt diets containing either low (0.4%) or high (1.6%) K with low (0.4%) and high (1.6%) Ca from age 1 to 4 mos. High oral K decreased BP independent of Ca intake (P < 0.05). High oral Ca did not affect BP. In contrast to aging SHRSP, high oral Ca neither increased urinary excretion nor decreased plasma concentration of K in these young adult SHRSP. However, high (vs. low) oral K only significantly reduced the half-maximal effective dose for acetylcholine-induced relaxation of aortic rings from rats fed low (18 +/- 3 vs. 38 +/- 6 nM, P < 0.05) not high Ca (25 +/- 5 vs. 31 +/- 3 nM). Neither oral K nor Ca affected nitroprusside-induced relaxation. Thus high oral Ca by itself does not impair endothelium-dependent relaxation in young adult high salt-fed SHRSP, but yet it suppresses the enhancing effect of high oral K on such relaxation and does so without altering BP, K balance, or endothelium-independent relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic social isolation in the prairie vole induces endothelial dysfunction: implications for depression and cardiovascular disease

“…First, the relaxant effects of ACh are expressed as relative (percent) not absolute changes in the PE-induced precontractions. This is common practice in all vascular contraction/relaxation experiments involving precontractions [35, 46, 48–50, 71–74] and is designed to correct for anticipated individual tissue differences in the absolute magnitude of the precontractile tensions. Second, the statistically significant attenuating effect of chronic social isolation on ACh-induced relaxation in the endothelium-intact tissues in question (Figure 2, left) is most noticeable at the maximum level of that relaxation (which occurred at the same ACh concentration, 10 −6 molar, in tissues from both paired and isolated animals).…”

“…Then the chest of each animal was opened, lungs and large veins discarded, residual blood in its cavity flushed out with cold physiological buffer, prepared as described previously [45], and the thoracic aorta removed with as much care as possible to minimize stretching. Unfortunately, some stretching was unavoidable as we found that the aorta in this animal was surrounded by considerably more connective and fat tissue than we have encountered in larger species [46]. The heart was also removed and weighed for later calculation of heart weight-to-body weight ratio.…”

“…After rinsing the same rings repeatedly with ACh-free buffer, they were treated again with multiple levels of ACh, except this time after first precontracting their smooth muscle with the selective alpha-1 adrenergic receptor agonist phenylephrine (PE). This allows evaluation of ACh-induced endothelium-dependent relaxation of such smooth muscle, due to stimulation of muscarinic receptors only in the endothelial layer [35], as widely conducted in aortic tissues from other species and usually expressed as % of the PE-induced precontraction [42, 46, 48–50]. We chose a PE concentration of 0.25 micromolar which in preliminary work caused nearly 50 % of maximum PE-induced contraction in our prairie vole aortas.…”

“…Finally, all the above aortic rings were rinsed repeatedly once more (with ACh- and PE-free buffer) and then, after precontracting again with PE, treated with multiple graded concentrations of the nitric oxide-donor NP to allow estimation of endothelium-independent relaxation of the underlying smooth muscle (also expressed as % of the PE-induced precontraction). NP is commonly employed for this purpose as a control measure for ACh relaxation tests in large conduit arteries like the aorta [46, 48–50]. In such vessels, the principal relaxing substance released by the endothelium in response to ACh is nitric oxide [52, 53].…”