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R Curtis Morris

Publications and source records attributed to R Curtis Morris.

6 recordsLinked to original sources

Relationship and interaction between sodium and potassium.

Compared with the Stone Age diet, the modern human diet is both excessive in NaCl and deficient in fruits and vegetables which are rich in K+ and HCO3- -yielding organates like citrate. With the modern diet, the K+/Na+ ratio and the HCO3-/Cl- ratio have both become reversed. Yet, the biologic machinery that evolved to process these dietary electrolytes remains largely unchanged, genetically fixed in Paleolithic time. Thus, the electrolytic mix of the modern diet is profoundly mismatched to its processing machinery. Dietary potassium modulates both the pressor and hypercalciuric effects of the modern dietary excess of NaCl. A marginally deficient dietary intake of potassium amplifies both of these effects, and both effects are dose-dependently attenuated and may be abolished either with dietary potassium or supplemental KHCO3. The pathogenic effects of a dietary deficiency of potassium amplify, and are amplified by, those of a dietary excess of NaCl and in some instances a dietary deficiency of bicarbonate precursors. Thus, in those ingesting the modern diet, it may not be possible to discern which of these dietary electrolytic dislocations is most determining of salt-sensitive blood pressure and hypercalciuria, and the hypertension, kidney stones, and osteoporosis they may engender. Obviously abnormal plasma electrolyte concentrations rarely characterize these dietary electrolytic dislocations, and when either dietary potassium or supplemental KHCO3 corrects the pressor and hypercalciuric effects of these dislocations, the plasma concentrations of sodium, potassium, bicarbonate and chloride change little and remain well within the normal range.

Acid-Base Imbalance↗

Chloride-dominant salt sensitivity in the stroke-prone spontaneously hypertensive rat.

We tested the hypothesis that in the stroke-prone spontaneously hypertensive rat (SHRSP), the Cl- component of dietary NaCl dominantly determines its pressor effect (salt-sensitivity). We telemetrically measured systolic aortic blood pressure (SBP) in SHRSP loaded with: nothing (CTL); NaCl alone (NaCl) (44 mmol/100 grams chow); KCl (KCl) alone (44 mmol); NaCl (44 mmol) combined with KHCO3 (77 mmol) (NaCl/KBC) or with KCl (77 mmol) (NaCl/KCl). Across all groups, from age 10 to 15 or 16 weeks, SBP increased linearly (mm Hg/week) (dp/dt, change in SBP as a function of time): CTL, 5.6; NaCl, 9.5; KCl, 8.8; NaCl/KBC, 9.1; and NaCl/KCl, 14.6. Thus, the value of dp/dt in KCl matched that in NaCl. The value of dp/dt in NaCl/KCl exceeded that in NaCl in direct proportion to the greater Cl- load. Across all groups, only Cl- load bore a direct, highly linear relationship with dp/dt. Strokes occurred only, but always with SBP >250 mm Hg, a value observed almost exclusively in NaCl/KCl. Thus, Cl- dominantly determined the pressor effect induced with dietary NaCl, both with NaCl loaded alone and combined with either KCl or KHCO3, and thereby likely determined the occurrence of stroke with NaCl loading. Over the initial 3-day period of NaCl loading and exacerbating hypertension, external balance of Na+ increased similarly among all groups. However, within 24 hours of initiating NaCl loading, urinary creatinine excretion decreased in direct proportion to dp/dt and urinary Cl- excretion. We conclude that in the SHRSP, the Cl- component of a dietary NaCl dominantly determines salt sensitivity and thereby phenotypic expression. We suggest that Cl- might do so by inducing renal vasoconstriction.

Animals↗

Long-term persistence of the urine calcium-lowering effect of potassium bicarbonate in postmenopausal women.

Potassium bicarbonate (KBC) potently reduces urine calcium excretion in adult humans, including patients with hypertension or calcium urolithiasis, and postmenopausal women. In the latter, who have substantial risk of calcium deficiency, it remains unknown whether the observed short-term urine calcium-lowering effect of KBC persists over years. We studied 170 postmenopausal women randomized to KBC 30, 60, or 90 mmol/d (KBC treatment), or placebo, for up to 36 months. Each received a multivitamin with 400 IU vitamin D, and calcium carbonate as needed to produce a total dietary calcium intake of at least 30 mmol daily. Daily urine calcium excretion (UCaV) did not differ among groups at baseline (all-groups mean +/- SD, 155 +/- 83 mg/d). From 1-36 months of KBC treatment, adjusting UCaV for creatinine (Cr) excretion, each dose of KBC reduced UCaV (P < 0.01) with a dose-dependent trend (P = 0.05). The reduced UCaV/Cr persisted throughout the KBC treatment period (up to 36 months) in all KBC, and the greatest reductions occurred in the subjects with greatest baseline UCaV/Cr (Delta UCaV/Cr vs. baseline UCaV/Cr; P < 0.001). Twenty-eight percent of the subjects had high baseline calciuria (UCaV/Cr > 200 mg Ca/1000 mg Cr). With baseline UCaV/Cr of 250 mg/1000 mg Cr, KBC 60 mmol decreased UCaV/Cr by 55.8 mg/1000 mg Cr, a potential daily calcium retention that over a 36-month period would accumulate up to 55,845 mg of calcium, nearly 5% of bone calcium content. KBC treatment induced a dose-dependent decrease in UCaV/Cr that persisted up to 36 months, with the greatest decreases occurring in those women with the greatest baseline UCaV, nearly a third of whom had high baseline calciuria. Thus, one can preselect postmenopausal women most likely to have the urine calcium-lowering effect of KBC and predict their potential bone calcium increase.

Adult↗

Chloride-dependent calcium transients induced by angiotensin II in vascular smooth muscle cells.

Cl- is essential for the vasoconstrictive response to angiotensin II (ANG II). In vascular smooth muscle cells (VSMC), we determined whether ANG II-induced transient increase in intracellular Ca2+ concentration ([Ca2+]i) is Cl- dependent. After incubating the cells at different extracellular Cl- concentration ([Cl-]e) for 40 min, the ANG II-induced Ca2+ transients at 120 meq/l Cl- were more than twice those at either 80 or 20 meq/l Cl-. Replacing Cl- with bicarbonate or gluconate yielded similar results. In addition, after removal of extracellular Ca2+, ANG II-induced as well as platelet-derived growth factor-induced Ca2+ release exhibited Cl- dependency. The difference of Ca2+ release with high vs. low [Cl-]e was not affected by acutely altering [Cl-]e 1 min before administration of ANG II when [Cl-]i was yet to be equilibrated with [Cl-]e. Pretreatment of a Cl- channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid, increased ANG II-induced Ca2+ release and entry at 20 meq/l Cl- but did not alter those at 120 meq/l Cl-. However, after equilibration, a reduced [Cl-]e did not affect thapsigargin-induced Ca2+ release, suggesting that Cl- may not affect the size of intracellular Ca2+ stores. Nevertheless, at high [Cl-], the peak increase of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] induced by ANG II was approximately sixfold that at low [Cl-]. Thus the Cl- -dependent effects of ANG II on Ca2+ transients may be mediated, at least in part, by a Cl- -dependent Ins(1,4,5)P3 accumulation in VSMC.

Angiotensin II↗

Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors.

BACKGROUND: Natural selection has had < 1% of hominid evolutionary time to eliminate the inevitable maladaptations consequent to the profound transformation of the human diet resulting from the inventions of agriculture and animal husbandry. OBJECTIVE: The objective was to estimate the net systemic load of acid (net endogenous acid production; NEAP) from retrojected ancestral preagricultural diets and to compare it with that of contemporary diets, which are characterized by an imbalance of nutrient precursors of hydrogen and bicarbonate ions that induces a lifelong, low-grade, pathogenically significant systemic metabolic acidosis. DESIGN: Using established computational methods, we computed NEAP for a large number of retrojected ancestral preagricultural diets and compared them with computed and measured values for typical American diets. RESULTS: The mean (+/- SD) NEAP for 159 retrojected preagricultural diets was -88 +/- 82 mEq/d; 87% were net base-producing. The computational model predicted NEAP for the average American diet (as recorded in the third National Health and Nutrition Examination Survey) as 48 mEq/d, within a few percentage points of published measured values for free-living Americans; the model, therefore, was not biased toward generating negative NEAP values. The historical shift from negative to positive NEAP was accounted for by the displacement of high-bicarbonate-yielding plant foods in the ancestral diet by cereal grains and energy-dense, nutrient-poor foods in the contemporary diet-neither of which are net base-producing. CONCLUSIONS: The findings suggest that diet-induced metabolic acidosis and its sequelae in humans eating contemporary diets reflect a mismatch between the nutrient composition of the diet and genetically determined nutritional requirements for optimal systemic acid-base status.

Acid-Base Equilibrium↗