Role of hypothalamic-renal noradrenergic systems in hypotensive action of potassium

T Fujita, Y Sato
1992 Hypertension  
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 noreplnephrine turnover, which was determined from the rate of decline of tissue norepinephrine concentration after the administration of ar-methyl-p-tyrosine, in 5-week-old SHR or age-matched Wistar-Kyoto (WKY) rats eating normal-NaCI (0.66%) or high-NaCI (8%)
more » ... t with supplementation of 8% KC1. 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 bat 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 a-methyi-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. The data suggest that hypothalamorenal noradrenergic systems might be involved in the hypotensive action of potassium in salt-loaded SHR. (Hypertension 1992;20:466-472) KEY WORDS • sympathetic nervous system • hypothalamus • norepinephrine • cold • potassium A ccumulating experimental evidence suggests that / \ dietary potassium intake plays an important A. \ -role in the regulation of blood pressure as well as in the pathogenesis of hypertension in animals and humans. 1 " 7 Moreover, the antihypertensive action of potassium might be linked to sodium intake; it could be exerted only under the condition of salt load since the supplementation of potassium attenuated salt-induced elevation of blood pressure in patients and animals with salt-sensitive hypertension, 2 -6 -8 but it did not affect blood pressure in the sodium-depleted state. 8 -9 According to the linkage to sodium, the main mechanism for potassium-induced antihypertensive action might be related to natriuresis, although the hypotensive action of potassium is still multifactorial. 1 -9 Evidence suggests that the increase in renal sympathetic nervous system (SNS) activity decreases urinary sodium excretion via both renal arteriolar vasoconstriction and increased tubular sodium reabsorption. 1011 Increased renal SNS activity was also involved in the development of hypertension through sodium retention in spontaneously hypertensive rats (SHR) since renal denervation promoted sodium excretion and delayed the development of hypertension. 12 Moreover, a recent study of Koepke and DiBona 13 showed that high NaCl intake produced a greater increase in renal SNS activity and a greater antinatriuresis induced by stressful environmental stimulation (air jet to head) in SHR but not in normotensive Wistar-Kyoto (WKY) rats. The data suggest that enhanced renal SNS activity and antinatriuretic response to air stress in SHR on high salt intake are dependent on a centrally mediated facilitation of sympathetic neural outflow to the kidney. Correspondingly, we demonstrated that potassium supplementation in deoxycorticosterone acetate-salt hypertensive rats attenuates the antinatriuretic and antidiuretic responses to air stress. 7 Moreover, it is consistent with the result of our previous experiment that potassium supplementation normalizes the abnormal renal and hypothalamic norepinephrine turnover in deoxycorticosterone acetate-salt rats. 3 Thus, potassium-induced attenuation of the increased renal SNS activity via the functional changes in the central noradrenergic mechanism may contribute to the antihypertensive action of potassium, possibly through natriuresis. Our recent study* demonstrated that potassium supplementation for 4 weeks in 5-week-old SHR, a model of human essential hypertension, attenuates the development of hypertension with salt loads by improvement of impaired renal function for sodium excretion. Because it is well known that the abnormalities of renal by guest on July 20, 2018 Downloaded from
doi:10.1161/01.hyp.20.4.466 pmid:1356921 fatcat:ic7ml6u7mvgylkmddb2vjnfkoe