Clinical and Experimental Pharmacology and Physiology (1992) 19,795-801

POTASSIUM ACCELERATES URINARY SODIUM EXCRETION DURING SALT LOADING WITHOUT STIMULATING ATRIAL NATRIURETIC POLYPEPTIDE SECRETION Masayuki Mano,* Akira Sugawara: Yasuo Nara,* Kazuwa Nakao? Ryoichi Horie,* Jiro Endo: Hiroo Imura and Yukio Yamori* *Department of Pathology and thboratory Medicine Shimane Medical University, Izumo and iDepartment of Internal Medicine, Kyoto University, School of Medicine, Kyoto, Japan (Received 5 June 1992)

SUMMARY 1. Effects of potassium (K) supplementation (100 mEq/day) on urinary sodium (Na) excretion and on the secretion of atrial natriuretic polypeptide (ANP) during salt loading (350 mEq/day) were studied in 12 healthy salt-resistant normotensives under strictly controlled metabolic ward conditions. 2. Urinary volume and Na excretion on the first day of the high salt period (HSP) were significantly greater in the K-supplemented group (KG) than in the control group (CG). 3. There was a significant gain in bodyweight after salt loading in both groups, with a significantly greater gain in CG on the second day of HSP. Haematocrit decreased significantly during salt loading in both groups, the degree of which was significantly greater in CG. 4. Plasma norepinephrine decreased significantly during salt loading in both groups, the degree of which was significantly less in KG than in CG. A significant increase in plasma ANP was observed in CG on and after the second day of HSP, while a significant increase in plasma ANP was observed on the fifth day of HSP in KG. 5. These findings indicate that K supplementation accelerates diuresis and natriuresis, resulting in moderate suppression of volume expansion induced by salt loading and that this accelerated diuresis and natriuresis is not a result of the action of ANP.

Key words: atrial natriuretic polypeptide, natriuresis, potassium, salt loading, volume expansion.

INTRODUCTION Recently more attention has been paid to preventative effects of potassium (K) against pernicious actions of dietary salt intake on blood pressure (BP) and stroke. Experimental evidence demonstrated that in strokeprone spontaneously hypertensive rat (SHRSP) salt augmented the development of hypertension but K attenuated it (Yamori 1981)and, further, K supplement-

ation prevented stroke in salt-loaded SHRSP (Tobian et al. 1984). Epidemiologically, our previous study in Japan (Yamori et al. 1981), the international cooperative study (WHO-CARDIAC Study) in People’s Republic of China (Yamori el al. 1986) and the INTERSALT study (Intersalt Co-operative Research Group 1988) demonstrated that BP was positively

Correspondence: Masayuki Mano, Department of Pathology, Shimane Medical University, Izumo 693, Japan.

M. Mano et al.

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related to the urinary sodium (Na) to K ratio. Possible interaction of these two electrolytes was also suggested by clinical observations in white and black normotensives (Luft et al. 1979) and in hypertensives (Fujita & Ando 1984). Two double-blind studies reported a small but significant fall in BP of hypertensives (MacGregor et al. 1982) and normotensives (Khaw & Thom 1982) after K supplementation, while some studies failed to demonstrate any significant changes in BP in hypertensives (Richards et al. 1984; Zoccali et al. 1985) and normotensives (Barden et al. 1986; Miller et al. 1987) after K supplementation. Although the mechanisms involved in the effect of K loading on BP are not yet fully understood, it has been suggested that diuresis and natriuresis induced by K loading may be responsible (Smith et al. 1983; Zoccali et al. 1985). Accumulating evidence shows that atrial natriuretic polypeptide (ANP) is a volume-regulatory hormone, causing natriuresis and diuresis in humans (Cole & Needleman 1985; Richards et al. 1985; Sugaware et al. 1985). Because both ANP and K have natriuretic action, it is possible that K intake elicits natriuresis through ANP secretion. However, there are only a few reports on this issue: one double-blind study showed that in free-living normotensive women K supplementation for 4 days induced natriuresis in spite of the slight reduction of plasma ANP (Barden et al. 1991). However, since the secretion of ANP should be minimal under the conditions they employed; that is, with normal Na intake, it remains of interest to find out whether ANP secretion is stimulated by K supplementation under salt-loading conditions, which require more potent activity of Na excretion. The purpose of the present study was to clarify the effect of K supplementation on urinary Na excretion during salt loading and the role of ANP in K-induced natriuresis. This study was performed in salt-resistant normotensives under strictly metabolic ward conditions.

METHODS Twelve male volunteers aged 21-29 years who had been confirmed to be salt-resistant normotensives in our previous salt-loading studies (Mano et al. 1987a, b) were recruited for the present study after approval according to the ethical regulation of Shimane Medical University. Informed consent was obtained from each volunteer after detailed explanation of the procedures to be performed. All volunteers underwent medical examination including blood tests and were confirmed

to be in good health without any significant medical history. Volunteers were divided into two groups and given experimental diets of identical regimen (2500 kcal/ day) for 10 days. During the initial 5 days both groups were given 60 mEq/ day of N a and 40 mEq/ day of K in diets (the low salt period; LSP). Dietary sodium was then increased by adding sodium chloride (NaC1; 350 mEq/day) in the diet (making a total intake of 410 mEq/day) in both groups (the high salt period; HSP) with additional K supplementation (KCl tablets, 100 mEq/day) only in one group. Dietary contents of protein, fat, carbohydrate, cholesterol and calcium were 90, 55, 410, 0.4 and 0.6 g/day, respectively, throughout the entire experimental period in both groups. Alcohol intake, smoking and strenuous physical activities that might increase electrolyte losses through sweating were strictly prohibited from 1 week before the study to the end of the study. BP was measured in the sitting position every day between 16:OO and 18:OO h before supper in all participants after resting for at least 20 min. An automatic sphygmomanometer (Khi, Vine International Co.), recording Korotkoff sound on thermal paper, was used in order avoid possible observer bias. This device was developed in our laboratory and validated in comparison with direct arterial pressure (Fukuoka et al. 1987). BP was measured blind in triplicate allowing enough intervals between cuff inflations to prevent venous congestion. Each recorded BP was read blind after the study was completed. The two lowest readings were averaged and mean arterial pressure was calculated as diastolic pressure plus onethird of pulse pressure. Twenty-four hour urine specimens were collected from all participants every day by using ‘aliquot cup’, simplified device to collect a portion (1/41.6) of 24 h urine (Nara e f al. 1984; Yamori et al. 1984). As a preservative, 0.5 mL of 6 N HC1 was placed in the urine container of the aliquot cup. Complete one-day specimens included the aliquot of all voided urine from the second urine in the morning to the first urine in the next morning. Urinary Na and K were measured within 24 h after collection. Blood samples were collected in the morning before breakfast every day in supine position after resting for at least 30 min to avoid postural effect on ANP. These samples were analysed for Na, K, haematocrit (Hct) and mean corpuscular volume (MCV). An aliquot of plasma was stored at - 80° C and then analysed for a-human ANP (a-hANP) using the radio-immunoassay described previously (Sugawara et al. 1985). Another blood sample for the determination of norepinephrine (NE) was collected in the morning on the third and

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Effect of potassium on ANP during salt load fifth days of each period in supine position after resting for 30 min through an indwelling catheter into the brachial vein. Bodyweight (BW) was measured every day before breakfast. No significant differences were observed in age, height, BW and BP between the two groups on the first day of LSP (P>0.05, t-test, Table 1). Further, no differences were observed in measured parameters between two groups on the fourth and the fifth days of LSP (P>0.05,t-test); therefore, averages of the values on the fourth and fifth days of LSP were used as the basal levels when compared with the values for HSP. Percentage changes were then calculated. Numerical data are expressed as mean Is.e.m. Within groups, the effect of salt loading was evaluated by one-way analysis of variance (ANOVA) for repeated measures and where this indicated a significant effect, differences from the basal levels were subsequently tested using the paired Student’s t-test. Significant differences between groups were tested by Student’s t-test.

Table 1. Characteristics of the CG and the KG on the first day of the LSP

Number Age (years) Height (cm) Weight (kg) Blood pressure (mmHg) Systolic Diastolic Mean

CG

KG

6 24.8 f 1 .O 172.7f 1.4 6 5 . 2 f 1.8

6 23.5 f0.8 171.5f0.9 65.8f3.4

115.5k6.0 72.2 5.6 86.6k 5.4

115.8k3.2 67.3 5 4.2 83.5 5.4

*

+

RESULTS BP showed no significant changes during HSP in either the control group (CG) or the K-supplemented group (KG) (P>0.05, ANOVA, Table 2). BW significantly increased during HSP in both groups (CG, P

Potassium accelerates urinary sodium excretion during salt loading without stimulating atrial natriuretic polypeptide secretion.

1. Effects of potassium (K) supplementation (100 mEq/day) on urinary sodium (Na) excretion and on the secretion of atrial natriuretic polypeptide (ANP...
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