Cardiovascular, endocrine, and body fluid-electrolyte responses to salt loading in mRen-2 transgenic rats.
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.
Li
P
P
Department of Physiology and Pharmacology and The Hypertension Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
Morris
M
M
Ferrario
C M
CM
Barrett
C
C
Ganten
D
D
Callahan
M F
MF
D000818:Animals; D030801:Animals, Genetically Modified; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D004837:Epinephrine / Q000097:blood; D005260:Female; D006579:Heterozygote; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D012982:Sodium, Dietary / Q000494:pharmacology*; D014667:Vasopressins / Q000097:blood / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
D012982:Sodium, Dietary; D014667:Vasopressins; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D012964:Sodium; D012083:Renin; D009638:Norepinephrine; D004837:Epinephrine