SYNERGISTIC VASCULAR EFFECTS OF DIETARY-SODIUM SUPPLEMENTATION AND ANGIOTENSIN-II ADMINISTRATION

The hypertensinogenic action of dietary sodium supplementation was inv estigated in angiotensin II (ANG II)-treated rats. We hypothesized tha t high-sodium diet would potentiate ANG II-induced vasoconstriction an d hypertension, including the development of structural vascular chang es, 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 periarter ial 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% N aCl diet (n = 6), or 0.7% NaCl diet (controls) (n = 10) for 12 wk. Sys tolic blood pressure (SBP) values were measured weekly for 4 wk and th en every other week for 8 wk. Then, the wall-to-lumen ratio (W/L) of m esenteric resistance arteries (<150 mu m OD) was measured after in sit u perfusion-fixation. After 7-10 days of treatment, there were no sign ificant changes in SBP in any of the groups. High-sodium diet increase d 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 trea tment further potentiated vasoconstrictor responses to ANG II (synergi sm). After 12 wk. of treatment, ANG II increased W/L of small resistan ce arteries by 11% (P < 0.05) without a significant rise in SBP. ANG I I 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 ob tained in control rats. To test the specificity of the interaction bet ween ANG II and high-sodium diet, all the experiments were repeated du ring phenylephrine (PE, 10 mu g . kg(-1) . min(-1) sc) treatment of ra ts. PE by itself or in combination with high-sodium diet had no effect on the measured parameters. Thus short-term administration of high-so dium diet appears to potentiate vasoconstrictor responses to ANG II by facilitating sympathetic neurotransmission, and long-term administrat ion of high-sodium diet raises SBP by potentiating the trophic vascula r effects of ANG II. The interaction appears to be specific to ANG II and is occurring on the vascular level.