High dietary phosphate intake induces hypertension and augments exercise pressor reflex function in rats

Abstract

An increasing number of studies have linked high dietary phosphate (Pi) intake to hypertension. It is well established that the rise in sympathetic nerve activity (SNA) and blood pressure (BP) during physical exertion is exaggerated in many forms of hypertension, which are primarily mediated by an overactive skeletal muscle exercise pressor reflex (EPR). However, it remains unknown whether high dietary Pi intake potentiates the EPR-mediated SNA and BP response to exercise. Accordingly, we measured renal SNA (RSNA) and mean BP (MBP) in normotensive Sprague-Dawley rats fed a normal Pi diet (0.6%, n = 13) or high Pi diet (1.2%, n = 13) for 3 mo. As previously reported, we found that resting BP was significantly increased by 1.2% Pi diet in both conscious and anesthetized animals. Activation of the EPR by electrically induced hindlimb contraction triggered greater increases in ΔRSNA and ΔMBP in the 1.2% compared with 0.6% Pi group (126 ± 25 vs. 42 ± 9%; 44 ± 5 vs. 14 ± 2 mmHg, respectively, P < 0.01). Activation of the muscle mechanoreflex, a component of the EPR, by passively stretching hindlimb muscle also evoked greater increases in ΔRSNA and ΔMBP in the 1.2% compared with 0.6% Pi group (109 ± 27 vs. 24 ± 7%, 38 ± 7 vs. 8 ± 2 mmHg, respectively, P < 0.01). A similar response was produced by hindlimb intra-arterial capsaicin administration to stimulate the metaboreflex arm of the EPR. Thus, our data demonstrate a novel action of dietary Pi loading in augmenting EPR function through overactivation of both the muscle mechanoreflex and metaboreflex.

A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human Subjects

“…These results are in accordance with all but one 28 report in normotensive and spontaneously hypertensive rats (both with normal renal function), that an HP diet elevated BP and augmented the exercise pressor reflex function. [29][30][31] Our studies also offer an explanation-at least in part-of the mechanism of the phosphate-induced hypertensinogenic effect: Although plasma renin/aldosterone concentrations and 24-hour excretion rates for both aldosterone and free cortisol were unchanged, 24-hour urinary excretion rates of metanephrine and normetanephrine increased significantly, explaining the additional observation of significantly increased mean 24-hour pulse rate. Even small increases in sympathetic nervous system activity may be sufficient to cause significant hypertension because an HP diet in mice has been reported to potentiate phenylephrineinduced vasoconstriction in ex vivo aortic rings.…”

Recombinant α-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy

“…Phosphotoxicity has received increasing attention as a pathogenic factor in the renal and extrarenai pathology in CKD. 41,42 α-Klotho deficiency results in phosphate retention, 11,17 and chronic high phosphate intake in rodents can compromise renal function even in the absence of CKD. 18 For unclear reasons and via unknown mechanisms, high phosphate intake paradoxically suppresses endogenous phosphaturic α-Klotho.…”

Integrated Assessment of Pharmacological and Nutritional Cardiovascular Risk Management: Blood Pressure Control in the DIAbetes and LifEstyle Cohort Twente (DIALECT)

“…We aim to address how well the targets for blood pressure management are reached, and how this is related to (1) pharmacological management; and (2) nutritional management (i.e., the dietary intake of salt [ 10 , 11 ], potassium [ 12 , 13 ], body mass index (BMI), and alcohol). Moreover, we assessed additional nutritional parameters for which no specific counselling was given, but have been shown to be relevant to cardiovascular risk in diabetic kidney disease (magnesium [ 14 , 15 , 16 ] and phosphate [ 17 , 18 ]). Because the presence of diabetic kidney disease implicates different blood pressure targets, we analysed patients without and with renal involvement separately.…”