Effects of high calcium diet on arterial smooth muscle function and electrolyte balance in mineralocorticoid‐salt hypertensive rats
Authors: Arvola Pertti , Ruskoaho Heikki , Pörsti Ilkka 
Published: July 2012

The effects of a high calcium diet (2.5%) on blood pressure, electrolyte balance, plasma and tissue atrial natriuretic peptide (ANP), cytosolic free Ca2+ concentration ([Ca2+]i), and arterial smooth muscle responses were studied in one‐kidney deoxycorticosterone (DOC)‐NaCl hypertensive Wistar rats.
Calcium supplementation for 8 weeks markedly attenuated the development of DOC‐NaCl hypertension and the associated cardiac hypertrophy, and prevented the DOC‐NaCl‐induced sodium‐volume retention as judged by reduced plasma Na+, and decreased plasma and ventricular ANP concentrations in high calcium‐fed DOC‐NaCl rats. However, calcium supplementation did not affect the DOC‐NaCl‐induced rise in platelet [Ca2+]i.
Smooth muscle contractions of isolated mesenteric arterial rings in response to depolarization by K+ (20–30 mm) were enhanced in DOC‐NaCl‐treated rats, this enhancement being abolished by concurrent oral calcium loading. The Ca2+ entry blocker nifedipine (10 nm) inhibited the contractions induced by K+ (30–125 mm) more effectively in DOC‐NaCl rats than in controls, while the inhibition in calcium‐loaded DOC‐NaCl rats was significantly greater than in controls only with 30 mm K+.
The contractions of mesenteric arterial rings induced by omission of K+ from the organ baths were used to evaluate cell membrane permeability to ions. In chemically denervated rings the onset of the gradual rise in contractile force in K+‐free medium occurred earlier, and the rate of the contraction was faster in DOC‐NaCl‐treated rats than in controls and high calcium‐fed DOC‐NaCl rats. Smooth muscle relaxation induced by 0.5 mm K+ upon K+‐free contractions was clearly slower in DOC‐NaCl rats than in controls and calcium‐supplemented DOC‐NaCl rats.
The functions of arterial smooth muscle Na+, Ca2+ exchange and Ca2+‐ATPase were evaluated by the aortic contractions elicited by low Na+ medium, and the subsequent relaxation responses induced by Ca2+‐free solution (in the presence of 5 mm caffeine, 1 μm nifedipine and 10 μm phentolamine). The rate of aortic low Na+ contractions (evaluating Ca2+ influx via Na+, Ca2+ exchange), as well as that of subsequent relaxations was slower in DOC‐NaCl‐treated rats than in controls, whether the relaxation was induced in normal (144.0 mm) or low (1.2 mm) organ bath Na+ concentration (reflecting Ca2+ extrusion by both Ca2+‐ATPase and Na+, Ca2+ exchange, and by Ca2+‐ATPase alone, respectively). However, in calcium‐supplemented DOC‐NaCl rats the aortic responses did not differ from control. The difference between the relaxation rate in normal and low Na+ concentration in each aortic ring, representing the contribution of Na+, Ca2+ exchange in these relaxations, was comparable in all groups.
In conclusion, calcium supplementation clearly attenuated the development of hypertension, cardiac hypertrophy, and sodium retention induced by the DOC‐NaCl treatment. However, the associated rise in platelet [Ca2+]i was not prevented, suggesting that in this form of experimental hypertension increased dietary calcium does not lower blood pressure by reducing [Ca2+]i. The results from vascular responses in vitro suggest that in arterial smooth muscle the DOC‐NaCl treatment increased contractile sensitivity to depolarization, voltage‐dependent Ca2+ entry and cell membrane permeability to ions, and attenuated relaxation responses and vascular Na+, K+‐ATPase function. The results further suggest reduced ability of the cell membrane to transport Ca2+ (possibly via Ca2+‐ATPase) in DOC‐NaCl hypertension. The high calcium diet opposed these alterations. The present results thus provide evidence that the antihypertensive effect of a high calcium diet in mineralocorticoid‐salt hypertension is mediated by its beneficial effects on systemic sodium balance and arterial smooth muscle function.