Prolonged dietary iron restriction alters total tissue iron but not heme iron: lack of impact on blood pressure and salt sensitivity
Twiddy, Matthew Ronald
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The World Health Organization (WHO) states that iron deficiency (ID) is the preeminent global micronutrient deficiency. Maternal ID is linked to cardiovascular disease and hypertension in offspring, and yet the impact of ID on the kidney is not known. We characterized the impact of ID on circulating and tissue levels of iron and renal function. Seven and ten week old male and female Wistar rats were fed either control (270ppm) or low iron (3ppm) diet for ten weeks. Total, non-heme and heme iron levels in liver, kidney cortex and kidney medulla were measured following the dietary period. Hematocrit decreased most in males regardless of age (Male 7-17wk: 47%→ 31%; 10-20wk: 47%→ 33.5%; Female 7-17wk: 47%→ 34%; 10-20wk: 47%→ 39%). Dietary ID markedly decreased liver and kidney cortex non-heme iron in both males and females (Female: liver-178±25 to 21±7 ppm; kidney cortex-51±9 ppm to 10±1 ppm; Male: liver-102±18 ppm to 11±1 ppm; kidney cortex 36±14 to 15±8 ppm). In contrast, non-heme iron in the kidney medulla was not significantly decreased Secondly, in order to determine the impact of ID on renal function, blood pressure was monitored using radio-telemetry starting at six weeks of age (~175g body weight). Dietary salt challenge (5 days Low5 days HighNormal) was administered to all animals (n=16) starting at eight weeks of age. At ten weeks rats were assigned to either control (225pm) or low (3ppm) iron diet. Dietary salt challenge was repeated at 13 and 18 weeks of age respectively. Despite significant lowering of hematocrit (Control 45% Low iron 38.6%) hemodynamic changes were minimal, in that, although blood pressure was lowered following ten weeks of dietary iron restriction, blood pressure did not change in response to dietary salt (Control MAP:105.0 ± 2.5mmHg; ID MAP:100.6 ± 3.2mmHg ). Collectively the tissue and functional analyses demonstrate that the body adapts to lowering of tissue iron supply with ID. The relative sparing of non-heme iron in the kidney medulla suggests that iron in this region of the kidney may be spared because of its importance in the systems responsible for regulating fluid and sodium balance.