Role of hypothalamic-renal noradrenergic systems in hypotensive action of potassium.
To clarify the role of the renal and hypothalamic noradrenergic systems in the antihypertensive actions of dietary potassium supplementation in salt-loaded spontaneously hypertensive rats (SHR), we measured systolic blood pressure and norepinephrine turnover, which was determined from the rate of decline of tissue norepinephrine concentration after the administration of alpha-methyl-p-tyrosine, in 5-week-old SHR or age-matched Wistar-Kyoto (WKY) rats eating normal-NaCl (0.66%) or high-NaCl (8%) diet with supplementation of 8% KCl. In WKY rats, neither high-sodium nor high-potassium diets had an effect on blood pressure with no change in renal or hypothalamic norepinephrine turnover. In SHR, however, salt loading accelerated the development of hypertension. Potassium supplementation did not affect blood pressure in normal-sodium SHR but attenuated the rise in blood pressure with salt loads. Correspondingly, renal norepinephrine turnover in SHR was increased compared with that of WKY rats, and salt loading further potentiated the increased turnover in the kidney; however, no changes in hypothalamic turnover occurred. Potassium supplementation attenuated the rise in blood pressure with salt loads and the increased renal turnover. Stimulation of sympathetic discharge by cold exposure after the administration of alpha-methyl-p-tyrosine produced marked depletion of norepinephrine in most tissues. The loss of norepinephrine was significantly greater in both kidney and hypothalamus of salt-loaded SHR than in those of normal-sodium SHR, but potassium could normalize this. Thus, potassium not only diminished the increased renal norepinephrine turnover in the kidney under normal conditions but also attenuated the augmented renal and hypothalamic norepinephrine turnover by cold stress in salt-loaded SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
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Fujita
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Sato
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003080:Cold Temperature; D006973:Hypertension / Q000503:physiopathology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012964:Sodium / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D019805:alpha-Methyltyrosine; D012964:Sodium; D014446:Tyrosine 3-Monooxygenase; D011188:Potassium; D009638:Norepinephrine