EFFECT OF POTASSIUM ON PLASMA RENIN CONCENTRATION IN THE PRESENCE AND ABSENCE OF ADH (BRATTLEBORO RAT MODEL)

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1 EFFECT OF POTASSIUM ON PLASMA RENIN CONCENTRATION IN THE PRESENCE AND ABSENCE OF ADH (BRATTLEBORO RAT MODEL) Emma Fernandez-Repollet, Susan Opava-Stitzer, and Manuel Martinez-Maldonado Department of Physiology University of Puerto Rico School of Medicine San Juan, Puerto Rico Rats with hereditary hypothalamic diabetes insipidus (so-called DI rats) have elevated plasma renin levels Although the mechanism responsible for this condition has not been elucidated, it seems reasonable to postulate that the absence of ADH 8 and/or the hypokalemia 4 previously reported in these rats might contribute to the elevation of plasma renin concentration (PRC). Evidence in favor of this hypothesis emerges from studies in which both ADH 6 and potassium 6 have been shown to inhibit renin release. In an attempt to examine the relative roles of ADH and potassium in the regulation of renin secretion, PRC was measured in OJ rats maintained on a potassium-free, normal potassium, or high potassium diet in the presence and absence of ADH treatment. Male and female OJ rats were used in all experiments. Body weights ranged from g. As depicted in TABLE 1, balance studies and PRC determinations were performed during a control period in four groups of untreated DI rats fed with a normal diet. Twenty-four-hour urine samples were collected for the measurement of urine volume, osmolality, and sodium and potassium concentrations. Plasma renin concentration was measured by radioimmunoassay of angiotensin I (AI, New England Nuclear). Following the control period, subgroups of six rats were placed for three weeks on the respective dietary regimen and/or AOH treatment; balance studies and PRC measurements were performed as previously described. Our data indicate that in the absence of AOH treatment PRC of OJ rats maintained on a K+-free diet (97 ± 11 ng AI/rnl/h) was not significantly different from that of DI rats maintained on a normal diet (98 ± 20 ng All ml/h). As illustrated in FIGURE 1, ADH treatment significantly diminished PRC of 01 rats maintained on a low or a normal potassium intake. Additionally, no significant difference between PRC of ADH-treated rats maintained on a normal or a low K+ diet (48 ± 6 vs. 71 ± 13 ng AI/ml/h) was detected. FIGURE 2 depicts the effect of a high potassium diet on PRC of DI rats in the absence of ADH treatment. It is evident from the results that a high K+ intake significantly reduced PRC of DI rats (74 ± 7 vs. 44± 6 ng All mllh, p < 0.01). This value of PRC was also significantly lower than that observed in control DI rats maintained concurrently on a normal potassium intake (109 ± 15, p < 0.01). As shown in FIGURE 3, PRC was found to be significantly lower in rats treated with both ADH and a high K+ diet (34 ± 3 ng AI/ml/h) than in rats treated with ADH alone (53 ± 5 ng AllmIlh, p < 0.01), suggesting an additive effect of potassium and ADH on PRC. As summarized in TABLE 2,

2 TABLE 1 EXPER~ENTAL PROTOCOL Control (Two weeks) (Three weeks) Experimental (Two weeks) Balance Study Balance Study Group 1 C N N N N HighK+ HighK+ Group 2 N OIL+N OIL+N N ADH+N ADH+N N ADH+HighK+ ADH+HighK+ Group 3 {i {: N* N* N* N* K+-Free K+-Free N* ADH+N* ADH+N* Group 4 {: N* ADH+K+-Free ADH+K+-Free N = Purina laboratory chow (K+: 0.92%); High K+ = Purina laboratory chow + 15 g KCI/I00 g of food; N * = K' free diet g KClIIOO g of food; and K+-Free = K+-free diet (General Biochemicals). FrOURE 1. Effect of ADH and a low potassium diet on plasma renin concentration in Dr rats. Bars to the left represent values in a control group maintained on a normal diet throughout the experiment. Bars to the right are values in the experimental group before and after a low K+ diet. ADH was administered to all rats in the experimental period. * Significantly different from values in the control period (p < 0.01).

3 J 10 D Control Period fa Experimental Period Norm"l Normal High Diet 1)let K Diet FIGURE 2. Effect of a high potassium diet on plasma renin concentration in Dr rats. Format is the same as in FIGURE 1. * Significantly different from values during the control period in the same rats or t from the control group (p < 0.01). 90 o Control Period ~ Experlmenta 1 Period 70 ~ E ;:,.. 50.s'" 0 2 & 30.. llr ADH (l00 mu/ioog BW) 10 Normal Diet Normal Diet High K Diet FIGURE 3. Effects of ADH and a high potassium diet on plasma renin concentration in Dr rats. For explanation see legend to FIGURE 1. * Significantly different from values obtained during a control period in the same rats or t from the control group (p < 0.01).

4 ADH treatment always reduced PRC in DI rats regardless of the potassium intake. The present study demonstrates that a:'k+-free diet did not increase PRe in DI rats; however, PRC of ADH-treated rats on a K+-free diet was higher than that of ADH-treated rats on a normal diet. Although the difference was not significant, such a tendency suggests that, in the presence of ADH, potassium deficiency might stimulate PRe in DI rats as in normal rats. In contrast, PRe in DI rats was significantly reduced on a high K+ intake. This finding is consistent with the inhibitory effect of potassium on PRC observed in other experimental animals. 7, S Since PRC of ADH-treated rats on a high potassium diet was significantly lower than that of ADH-treated rats on a normal diet, one might speculate that the effects of these two inhibitors on renin release are additive and probably have different mechanisms of action. As in other studies 1, 2 ADH administration significantly decreased PRC of DI rats on a normal diet. Although the present study has not dealt with the mechanism by which ADH or potassium inhibits renin release, several actions might be postulated, e.g. a direct action of either ADH or potassium on the granular cells or the renal baroreceptor, an indirect action of potassium mediated through changes TABLE 2 PLASMA RENIN CONCENTRATION IN ADH-TREATED DI RATS ON VARYING POTASSIUM INTAKES (ng Allml/h) NormalK+ HighK+ Dr 97±11 74±16 44±5 Dr +ADH 71±13* 53±5 * 34±3 * Values presented as mean ± SEM; * p < in sodium delivery to the macula densa, or indirect effects of ADH as a result of water or sodium retention. Finally, the fact that ADH treatment consistently diminished PRC in DI rats regardless of the potassium intake strongly suggests that the absence of ADH either directly or indirectly is the principal factor involved in the elevated PRC characteristic of DI rats. REFERENCES 1. GROSS, F., G. DAUDA, S. KAZDA, J. KYNCL, J. MOHRING & H. ORTH Increased fluid turnover and the activity of the renin-angiptensin system under various experimental conditions. Circ. Res (Supp!. IT): GUTMAN, Y. & F. BENZAKEIN Antidiuretic hormone and renin in rats with diabetes insipidus. Eur. J. Pharmacol. 28: VALTIN, H. & H. A. SCHROEDER Familial hypothalamic diabetes insipidus in rats (Brattleboro strain). Am. J. Physio!. 206: MOHRING, B., 1. MOHRING, G. DAUDA & D. HAACK Potassium deficiency in rats with hereditary diabetes insipidus. Am. J. Physio!. 297:

5 5. OPARIL, S. & E. HARBER The renin-angiotension system. N. Eng!. 1. ~ed.291: DAVIS, J. O. & R. H. FREEMAN ~echanisms regulating renin release. Physio!. Rev. 56( 1): SEALEY, J. E.,!. CLARK, ~. B. BULL & J. H. LARAGH Potassium balance and the control of renin secretion. J. Clin. Invest. 49: FLAMENBAUM, W., J. G. KLEINMAN, 1. S. ~CNEIL, R. J. HAMBURGER & T. A. KOTCHEN Effect of KCI infusion on renin secretion and aldosterone excretion in dogs. Am. J. Physio!. 229: