RESUMEN
BACKGROUND: In the stroke-prone spontaneously hypertensive rat (SHRSP) fed a low-normal NaCl diet, we recently reported that supplemental KCl, but not KHCO(3) or K-citrate (KB/C), exacerbated hypertension and induced hyperreninemia and strokes. We now ask the following question: In these SHRSP, is either such selectively Cl(-)-sensitive hypertension or hyperreninemia a pathogenetic determinant of renal microvasculopathy? METHODS: SHRSPs were randomized to either supplemental KCl, KB/C, or nothing (control) at 10 weeks of age. Four and 14 weeks afterward, we assessed renal microangiopathy histologically and measured plasma renin activity (PRA). From randomization, blood pressure was measured radiotelemetrically and continually; proteinuria was measured periodically. RESULTS: KCl, but not KB/C, amplified renal microangiopathy and proteinuria. Four weeks after randomization, when KCl initially exacerbated hypertension, renal microangiopathy, hyperproteinuria, and hyperreninemia had not yet occurred. However, across all groups, the increment of SBP at four weeks strongly predicted its final increment, severity of renal microangiopathy, proteinuria, and PRA 14 weeks after randomization. Then, the severity of renal microangiopathy varied directly with the levels of systolic blood pressure (SBP; R(2) = 0.9, P < 0.0001), PRA (R(2) = 0.7, P < 0.0001), and proteinuria (R(2) = 0.8, P < 0.0001) as continuous functions across all treatment groups. Renal creatinine clearance was greater with KB/C. CONCLUSIONS: In the SHRSP, (1) like cerebral microangiopathy, renal microangiopathy is selectively Cl(-) sensitive and hence, systemic microangiopathy is as well; (2) Cl(-) likely amplifies microangiopathy by exacerbating hypertension and possibly also by increasing PRA; and (3) Cl(-) might increase blood pressure and PRA by further constricting the renal afferent arteriole.
Asunto(s)
Cloruros/farmacología , Hipertensión/complicaciones , Ratas Endogámicas SHR/fisiología , Circulación Renal/efectos de los fármacos , Accidente Cerebrovascular/etiología , Enfermedades Vasculares/fisiopatología , Animales , Bicarbonatos/farmacología , Presión Sanguínea/efectos de los fármacos , Creatinina/metabolismo , Susceptibilidad a Enfermedades , Hipertensión/fisiopatología , Masculino , Microcirculación/efectos de los fármacos , Cloruro de Potasio/farmacología , Citrato de Potasio/farmacología , Compuestos de Potasio/farmacología , Proteinuria/orina , Ratas , Renina/sangre , Índice de Severidad de la Enfermedad , Enfermedades Vasculares/orinaRESUMEN
Compared to the prehistoric diet, the modern human diet contains not only excessive NaCl and deficient K+, but also deficient precursors of HCO3- and sometimes excessive precursors of nonvolatile acid. The mismatch between the modern diet and the still ancient biological machinery of humans subtly but chronically disorders their internal milieu, giving rise to a prolonged state of low-grade potassium deficiency and low-grade metabolic acidosis whose severity increases with age. Supplemental KCI cannot redress this mismatch and correct this state. However, the mismatch is redressed and the state corrected by restoring intakes of K+ and HCO3- to levels approaching those in the diet of our prehistoric forebearers, with either fruits and vegetables or with supplemental KHCO3. So restored, KHCO3 can: 1) attenuate hypertension and possibly prevent its occurrence by suppressing the phenomenon of normotensive NaCl-sensitivity, in part by its natriuretic effect; (2) prevent kidney stones by reducing urinary excretion of calcium and increasing urinary excretion of citrate; (3) ameliorate and protect against the occurrence of osteoporosis by increasing the renal retention of calcium and phosphorus, and by suppressing bone resorption and enhancing bone formation; and (4) likely prevent stroke.
Asunto(s)
Bicarbonatos/metabolismo , Suplementos Dietéticos , Hipertensión/prevención & control , Osteoporosis/prevención & control , Cloruro de Potasio/metabolismo , Compuestos de Potasio/metabolismo , Potasio en la Dieta/metabolismo , Accidente Cerebrovascular/prevención & control , Adulto , Animales , Bicarbonatos/administración & dosificación , Niño , Preescolar , Humanos , Persona de Mediana Edad , Cloruro de Potasio/administración & dosificación , Compuestos de Potasio/administración & dosificación , Potasio en la Dieta/administración & dosificación , Pronóstico , RatasRESUMEN
In 16 African Americans (blacks, 14 men, 2 women) with average admission mean arterial pressure (MAP, mm Hg) 99.9+/-3.5 (mean+/-SEM), we investigated whether NaCl-induced renal vasoconstriction attends salt sensitivity and, if so, whether supplemental KHCO3 ameliorates both conditions. Throughout a 3-week period under controlled metabolic conditions, all subjects ate diets containing 15 mmol NaCl and 30 mmol potassium (K+) (per 70 kg body wt [BW] per day). Throughout weeks 2 and 3, NaCl was loaded to 250 mmol/d; throughout week 3, dietary K+ was supplemented to 170 mmol/d (KHCO3). On the last day of each study week, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) using renal clearances of PAH and inulin. Ten subjects were salt sensitive (SS) (DeltaMAP >+5%) and 6 salt resistant (SR). In NaCl-loaded SS but not SR subjects, RBF (mL/min/1.73 m2) decreased from 920+/-75 to 828+/-46 (P<0.05); filtration fraction (FF, %) increased from 19. 4+/- to 21.4 (P<0.001); and renal vascular resistance (RVR) (10(3)xmm Hg/[mL/min]) increased from 101+/-8 to 131+/-10 (P<0.001). In all subjects combined, DeltaMAP varied inversely with DeltaRBF (r =-0.57, P=0.02) and directly with DeltaRVR (r = 0.65, P=0.006) and DeltaFF (r = 0.59, P=0.03), but not with MAP before NaCl loading. When supplemental KHCO3 abolished the pressor effect of NaCl in SS subjects, RBF was unaffected but GFR and FF decreased. The results show that in marginally K+-deficient blacks (1) NaCl-induced renal vasoconstrictive dysfunction attends salt sensitivity; (2) the dysfunction varies in extent directly with the NaCl-induced increase in blood pressure (BP); and (3) is complexly affected by supplemented KHCO3, GFR and FF decreasing but RBF not changing. In blacks, NaCl-induced renal vasoconstriction may be a pathogenetic event in salt sensitivity.
Asunto(s)
Bicarbonatos/administración & dosificación , Población Negra/genética , Compuestos de Potasio/administración & dosificación , Circulación Renal/efectos de los fármacos , Cloruro de Sodio Dietético/administración & dosificación , Vasoconstricción/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Hemodinámica/genética , Humanos , Masculino , Circulación Renal/genéticaRESUMEN
-Normotensive salt sensitivity, a putative precursor of hypertension, might be quite frequent in African Americans (blacks) and less frequent in Caucasian Americans (whites), but only when dietary potassium is deficient and not when maintained well within the normal range. We tested this hypothesis in 41 metabolically controlled studies of 38 healthy normotensive men (24 blacks, 14 whites) who ate a basal diet low in sodium (15 mmol/d) and marginally deficient in potassium (30 mmol/d) for 6 weeks. Throughout the last 4 weeks, NaCl was loaded (250 mmol/d); throughout the last 3, potassium was supplemented (as potassium bicarbonate) to either mid- or high-normal levels, 70 and 120 mmol/d. Salt sensitivity, defined as an increase in mean arterial blood pressure >/=3 mm Hg with salt loading, was deemed "moderate" if increasing =10 mm Hg and "severe" if increasing more. When dietary potassium was 30 mmol/d, salt loading induced a mean increase in blood pressure only in blacks (P<0.001), and salt sensitivity occurred in most blacks but not whites (79% vs 36% (P<0.02). Supplementing potassium only to 70 mmol/d attenuated moderate salt sensitivity similarly in blacks and whites; 120 mmol/d abolished it, attenuated severe salt sensitivity, which occurred in a quarter of affected blacks, and suppressed the frequency and severity of salt sensitivity in blacks to levels similar to those observed in whites. These observations demonstrate that in most normotensive black men but not white men, salt sensitivity occurs when dietary potassium is even marginally deficient but is dose-dependently suppressed when dietary potassium is increased within its normal range. Such suppression might prevent or delay the occurrence of hypertension, particularly in the many blacks, in whom dietary potassium is deficient.
Asunto(s)
Presión Sanguínea , Hipertensión/etiología , Deficiencia de Potasio/complicaciones , Potasio en la Dieta , Grupos Raciales , Cloruro de Sodio Dietético/efectos adversos , Adulto , Anciano , Bicarbonatos/administración & dosificación , Población Negra , Interpretación Estadística de Datos , Humanos , Hipertensión/prevención & control , Modelos Lineales , Masculino , Persona de Mediana Edad , Compuestos de Potasio/administración & dosificación , Potasio en la Dieta/administración & dosificación , Cloruro de Sodio Dietético/administración & dosificación , Población BlancaRESUMEN
Acute vasopressor responses to stress are adrenergically mediated and hence potentially subject to differential modulation by dietary potassium and sodium. The greater vasopressor responsiveness in blacks compared with whites might then be consequent not only to a high dietary salt intake but also to a marginally reduced dietary potassium intake. Under controlled metabolic conditions, we compared acute vasopressor responses to cold and mental stress in black and white normotensive men during three successive dietary periods: (1) while dietary potassium was reduced (30 mmol K+/70 kg per day) and salt was restricted (10 to 14 days); (2) while salt was loaded (15 to 250 mmol Na+/70 kg per day) (7 days); and (3) while salt loading was continued and potassium was either supplemented (70 mmol K+/70 kg per day) (7 to 21 days) in 9 blacks and 6 whites or continued reduced (30 mmol K+/70 kg per day) (28 days) in 4 blacks (time controls). At the lower potassium intake, cold-induced increase in forearm vascular resistance in blacks was twice that in whites during both salt restriction and salt loading. Normalization of dietary potassium attenuated cold-induced increases in both forearm vascular resistance and systolic and diastolic blood pressures in blacks but only in systolic pressure in whites. In blacks but not in whites, normalization of dietary potassium attenuated mental stress-induced increases in systolic and diastolic pressures. In normotensive blacks but not whites, a marginally reduced dietary intake of potassium reversibly enhances adrenergically mediated vasopressor responsiveness to stress. That responsiveness so enhanced over time might contribute to the pathogenesis of hypertension in blacks.
Asunto(s)
Población Negra , Potasio en la Dieta/administración & dosificación , Potasio/fisiología , Estrés Fisiológico , Resistencia Vascular/fisiología , Población Blanca , Adulto , Presión Sanguínea/fisiología , Humanos , Masculino , Estrés Fisiológico/genética , Estrés Fisiológico/metabolismo , Estrés Fisiológico/fisiopatologíaRESUMEN
The stroke-prone spontaneously hypertensive rat (SHRSP) is a genetically determined model of "salt-sensitive" stroke and hypertension whose full phenotypic expression is said to require a diet high in Na+ and low in K+. We tested the hypothesis that dietary Cl- determines the phenotypic expression of the SHRSP. In the SHRSP fed a normal NaCl diet, supplementing dietary K+ with KCl exacerbated hypertension, whereas supplementing either KHCO3 or potassium citrate (KB/C) attenuated hypertension, when blood pressure (BP) was measured radiotelemetrically, directly and continually. Supplemental KCl, but not KB/C, induced strokes, which occurred in all and only those rats in the highest quartiles of both BP and plasma renin activity (PRA). PRA was higher with KCl than with KB/C. These observations demonstrate that with respect to both severity of hypertension and frequency of stroke the phenotypic expression of the SHRSP is (i) either increased or decreased, depending on whether the anionic component of the potassium salt supplemented is, or is not, Cl-; (ii) increased by supplementing Cl- without supplementing Na+, and despite supplementing K+; and hence (iii) both selectively Cl--sensitive and Cl--determined. The observations suggest that in the SHRSP selectively supplemented with Cl- the likelihood of stroke depends on the extent to which both BP and PRA increase.
Asunto(s)
Trastornos Cerebrovasculares/genética , Hipertensión/genética , Cloruro de Sodio Dietético/metabolismo , Animales , Trastornos Cerebrovasculares/metabolismo , Hipertensión/metabolismo , Ratas , Ratas Endogámicas SHR , Cloruro de Sodio Dietético/administración & dosificaciónRESUMEN
A review of published research data on the requirement, intake, and signs of deficiency of vitamins and trace elements in old age is presented. It particularly deals with the problem of a general indication for vitamins and trace element supplements - the mean components of geriatric preparations. Special emphasis is laid on the question if these substances exhibit a specific effect on the alterations of physical and psychic capacity typically accompanying the growing old. It could be shown that in several groups of the elderly diminished vitamin levels are common and/or vitamin and trace element intake does not reach daily recommended allowances. But it still remains unclear if these findings have to be considered as disease symptoms.