title: Synergistic vascular effects of dietary sodium supplementation and angiotensin II administration.
abstract: The hypertensinogenic action of dietary sodium supplementation was investigated in angiotensin II (ANG II)-treated rats. We hypothesized that high-sodium diet would potentiate ANG II-induced vasoconstriction and hypertension, including the development of structural vascular changes, through synergistic action with ANG II in stimulating sympathetic activity and vascular growth. Mesenteric vasoconstrictor responses to ANG II, norepinephrine (NE), arginine vasopressin (AVP), and periarterial nerve stimulation were measured in Sprague-Dawley rats after 7-10 days of the following treatments: 200 ng.kg-1.min-1 ip ANG II (n = 12), 4% NaCl diet (n = 11), ANG II + 4% NaCl diet (n = 7), and 0.7% NaCl diet (controls) (n = 15). Additional rats received 50 ng.kg-1.min-1 sc ANG II (n = 8), 2% NaCl diet (n = 9), ANG II + 2% NaCl diet (n = 6), or 0.7% NaCl diet (controls) (n = 10) for 12 wk. Systolic blood pressure (SBP) values were measured weekly for 4 wk and then every other week for 8 wk. Then, the wall-to-lumen ratio (W/L) of mesenteric resistance arteries (< 150 microns OD) was measured after in situ perfusion-fixation. After 7-10 days of treatment, there were no significant changes in SBP in any of the groups. High-sodium diet increased vasoconstrictor responses to ANG II (P < 0.01) and nerve stimulation (P < 0.02), but not to NE or AVP, and in combination with ANG II treatment further potentiated vasoconstrictor responses to ANG II (synergism). After 12 wk of treatment, ANG II increased W/L of small resistance arteries by 11% (P < 0.05) without a significant rise in SBP. ANG II and 2% NaCl diet in combination raised SBP by 36 mmHg (P < 0.01) and increased small artery W/L by 28% (P < 0.001) compared with values obtained in control rats. To test the specificity of the interaction between ANG II and high-sodium diet, all the experiments were repeated during phenylephrine (PE, 10 micrograms.kg-1.min-1 sc) treatment of rats. PE by itself or in combination with high-sodium diet had no effect on the measured parameters. Thus short-term administration of high-sodium diet appears to potentiate vasoconstrictor responses to ANG II by facilitating sympathetic neurotransmission, and long-term administration of high-sodium diet raises SBP by potentiating the trophic vascular effects of ANG II. The interaction appears to be specific to ANG II and is occurring on the vascular level.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, Minneapolis, Minnesota, USA.
authors.forename: B
authors.initials: B
authors.lastname: Csiky
authors.forename: G
authors.initials: G
authors.lastname: Simon
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D004357:Drug Synergism; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D012982:Sodium, Dietary; D000804:Angiotensin II; D010656:Phenylephrine