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Department of Physiology and Pharmacology and The Hypertension Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083; and Max Delbruck Center for Molecular Medicine, 01115 Berlin-Buch, Germany
We previously
demonstrated that mRen-2 transgenic [Tg(+)] rats are
sensitive to chronic high NaCl intake, showing increased arterial
pressure and vasopressin (VP) secretion. In this study, we determined
the effect of a chronic osmotic challenge, 4 days of drinking 2% NaCl,
on direct arterial blood pressure, heart rate, fluid-electrolyte
balance, circadian rhythm of mean arterial pressure (MAP), and changes
in plasma VP and catecholamines. Under baseline conditions, male Tg(+)
rats showed a significant shift in the peak in circadian MAP into the
light portion of the day-night cycle. Substitution of 2% NaCl for
drinking water caused a rapid increase in MAP, 20 ± 5 mmHg in Tg(+)
rats within 6 h. Whereas the amplitude of circadian MAP fluctuations
increased in salt-loaded Tg(+) rats, there was no significant change in
the circadian timing of peak MAP with salt loading. Tg(+) rats showed
exaggerated osmotic-induced increases in plasma VP, norepinephrine
(NE), and epinephrine (Epi) compared with Tg(
) rats. Plasma NE
and Epi were increased two- and fourfold, respectively, in the
hypertensive rats with no significant change in the Tg(
) rats.
Intravenous administration of a VP antagonist did not alter arterial
pressure in either Tg(+) or Tg(
) rats. Tg(+) and Tg(
)
rats showed a positive sodium balance with no significant difference
observed between the groups. Tg(+) rats showed a significant increase
in salt consumption, plasma sodium, osmolality, and hematocrit,
accompanied by a negative water balance. We conclude that Tg(+) rats
are sensitive to acute and chronic osmotic stimuli in terms of blood
pressure, fluid-electrolyte balance, and plasma VP and catecholamines.
Whereas elevated plasma VP does not contribute to the hypertensive
response, increased sympathetic drive may mediate the salt-induced
blood pressure changes in this model.
hypertension; renin; vasopressin; catecholamines; osmotic challenge
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