Reversal of hypertension and endothelial dysfunction in
deoxycorticosterone-nacl-treated rats by high calcium diet.
M[umlaut]akynen, Heikki, Mika K[umlaut]ah[diaeresis]onen, Xiumin Wu,
Heikki Wuorela, and Ilkka P[diaeresis]orsti.
Department of Pharmacology, Clinical Pharmacology and Toxicology
Medical School, University of Tampere, P.O. Box 607,FIN-33101
Tampere, Finland and Departments of Clinical Physiology and Internal
Medicine, Tampere University Hospital, P.O. Box 2000, FIN-33521
Tampere, Finland
APStracts 2:0421H, 1995.
We tested the hypothesis whether high calcium diet could favourably
affect blood pressure and arterial function in established
deoxycorticosterone (DOC)-NaCl hypertension. Therefore, calcium
supplementation of Wistar rats was commenced 8 weeks after the
initiation of DOC-NaCl treatment. High calcium intake (2.5 %; group
Ca-DOC) for 4 weeks reversed the development of hypertension, whereas
in animals ingesting normal diet (1.1 % calcium; group DOC) blood
pressure continued to rise. Responses of mesenteric arterial rings in
vitro were examined at the end of the 12 week study. In
norepinephrine (NE)-precontracted arterial rings endothelium
dependent relaxations to acetylcholine (ACh) and ADP as well as
endothelium independent relaxations to nitroprusside were attenuated
in the DOC group, while all these responses were significantly
improved by calcium supplementation. The nitric oxide (NO) synthesis
inhibitor NG nitro L arginine methyl ester (L-NAME), in the presence
of the cyclo-oxygenase inhibitor diclofenac, totally abolished ACh
-induced relaxations in the DOC group but only attenuated them in the
Ca-DOC group. This L-NAME and diclofenac resistant relaxation was
partially (by about 40 %) prevented by apamin, an inhibitor of Ca2+
activated K+ channels. Further addition of glyburide, a blocker of
ATP dependent K+ channels, practically abolished the residual
relaxations to ACh in the Ca-DOC group. Interestingly, when
endothelium-dependent hyperpolarization (EDHF) was prevented by
precontracting the preparations with KCl (50 mM), no differences were
found in relaxations to ACh and ADP between the groups. Furthermore,
arterial contractions to NE and KCl, as well as the increase in
contractile sensitivity to these agonists induced by NO synthesis
inhibition, were comparable in the DOC and Ca DOC groups. In
conclusion, high calcium diet effectively reduced blood pressure in
established two kidney DOC NaCl hypertension and concomitantly
enhanced arterial relaxation. Since the relaxations to ACh and ADP in
the Ca DOC group were augmented in the absence and presence of NO
synthesis inhibition, but not under conditions of prevented
hyperpolarization, these enhanced relaxations could be attributed to
promoted endothelium dependent hyperpolarization in the calcium
supplemented animals.
Received 28 April 1995; accepted in final form 12 September 1995.
APS Manuscript Number H401-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95