The effect of potassium loading and sodium depletion on DOC induced hypertension in sheep

Abstract

Abstract. This study examines the physiological effects of 1 1-deoxycorticosterone (DOC) at 2 rates of continuous iv infusion for 5 days in conscious sheep. DOC treatment, in sheep on Na and K intake 80 and 120 mmol/day respectively, increased mean arterial pressure (MAP) by 12 mmHg at 50 mg/day and by 10 mmHg at 5 mg/day. Both rates of infusion raised plasma [Na] and lowered plasma [K]. Urinary Na excretion fell on the first day of infusion. On cessation of infusion there was a natriuresis. A high K intake of approximately 800 mmol/day for 7 to 10 days prior to and during DOC (5 mg/day) treatment abolished the rise in blood pressure, the rise in plasma [Na], the intitial Na retention and the post-DOC natriuresis. Plasma [K] rose with high K intake and fell with DOC. Na depletion prior to DOC infusion (5 mg/day) prevented the rise in MAP. Urinary Na excretion remained low and plasma [K] fell. This study shows that K loading abolishes DOC hypertension in sheep by a mechanism which may involve modification of the Na retaining effects of the steroid.

The effect of sodium depletion and potassium loading on cortisol induced hypertension in sheep

“…The sheep depleted of 300-500 Na+ mmol were analysed separately, and this degree of depletion also reduced cortisol hypertension. Acute Na+ depletion blocked DOC hypertension in the sheep (Na+ loss 580 ±110 mmol) (Mills et al 1984a), but not ACTH hyper¬ tension (Na+ loss 476 ± 46 mmol) ). However, with profound Na+ loss (500-900 mmol) hypertension of all types may be blocked because of fluid volume contraction.…”

“…hypertension in rats on a Na+ restricted diet or in Na depleted sheep (Mills et al 1984a). Although mineralocorticoid hypertension is regarded ge¬ nerally as Na+-dependent, glucocorticoid hyper¬ tension is accepted on the other hand as being independent of Na+ status.…”

“…Glucocorticoid induced hypertension developed in rats on,, a Na + 're¬ stricted diet (Knowlton et al 1952), whereas mineralocorticoids (such as DOC) do not produce hypertension in rats on a Na+ restricted diet or in Na depleted sheep (Mills et al 1984a). Although mineralocorticoid hypertension is regarded ge¬ nerally as Na+-dependent, glucocorticoid hyper¬ tension is accepted on the other hand as being independent of Na+ status.…”

“…The effect of KC1 loading on steroid hypertension is not clear. A high K+ intake has been reported to prevent and reduce the mine¬ ralocorticoid hypertension produced by deoxycorticosterone (DOC) (Sato et al 1982;Suzuki et al 1981b;Mills et al 1983Mills et al , 1984a), but Rosenman et al (1951) found that a high K+ intake had no effect on DOC hypertension. It has been postula¬ ted that K+ loading abolished DOC hypertension by a mechanism involving increased urinary Na+ excretion (Mills et al 1983;Sato et al 1982;Suzuki et al 1981b).…”

“…In contrast, uncompensated acute Na+ depletion increased peripheral resistance, re¬ duced cardiac output and extracellular fluid vol¬ ume and plasma volume, and reduced pressor responsiveness to angiotensin II(Coghlan et al 1977;McDougall et al 1978;Mason et al 1984). K+ loading was effective in blocking DOC hyper¬ tension in sheep(Mills et al 1984a), but did not reduce 9a-fiuorocortisol (2 mg/day) hypertension in the sheep, whereas Na+ depletion was effective in reducing both DOC and 9ct-fluorocortisol hypertension(Mills et al 1984a,b;Whitworth et al 1986). These results suggested that in the…”