H. Makynen et al., ENDOTHELIAL FUNCTION IN DEOXYCORTICOSTERONE NACL HYPERTENSION - EFFECT OF CALCIUM SUPPLEMENTATION, Circulation, 93(5), 1996, pp. 1000-1008
Background Dietary calcium intake has been suggested to correlate inve
rsely with blood pressure in humans and experimental animals. However,
the effects of calcium supplementation on hypertensive disturbances o
f the endothelium have nor been well characterized. Methods and Result
s Wistar-Kyoto rats were made hypertensive by deoxycorticosterone (DOC
)-NaCl treatment, but a concurrent increase in chow calcium content fr
om 1.1% to 2.5% markedly attenuated the rise in blood pressure. The fu
nction of isolated mesenteric arterial rings in vitro was investigated
at the close of the 10-week study. In norepinephrine-precontracted ri
ngs, the relaxations to acetylcholine (ACh) and ADP, as well as to nit
roprusside, 3-morpholinosydnonimine, and isoploterenol were attenuated
in hypertensive rats on 1.1% calcium, but these responses were improv
ed by calcium supplementation. In the presence of NG-nitro-L-arginine
methyl ester (L-NAME), the relaxations to ACh in hypertensive animals
on normal calcium were practically absent, whereas in normotensive rat
s and calcium-supplemented hypertensive rats, distinct relaxations to
higher concentrations of ACh were still present. These responses were
reduced by 30% to 50% with apamin, a blocker of Ca2+-activated K+ chan
nels, and were further inhibited by blockade of ATP-dependent K+ chann
els with glyburide. Interestingly, relaxations elicited by ACh and ADP
during precontraction with 60 mmol/L KCl (preventing endothelium-depe
ndent hyperpolarization) were not impaired in hypertensive animals. Th
e contractile sensitivity of endothelium-intact arterial rings to 5-hy
droxytryptamine and norepinephrine was higher in hypertensive rats on
either normal or high-calcium diet, whereas the increase in contractil
e sensitivity caused by L-NAME corresponded in all groups. Conclusions
High-calcium diet markedly opposed experimental DOC-NaCl hypertension
, an effect associated with improved arterial relaxation, while abnorm
alities of vascular contractile properties remained unaffected. In par
ticular, the hyperpolarization-related component of endothelium-depend
ent arterial relaxation, mediated via opening of arterial K+ channels,
could be augmented by calcium supplementation in DOC-NaCl hypertensio
n.