RESUMO
This study was undertaken to evaluate the effect of chronic diuretic therapy with chlorothiazide on the course of salt hypertension in hypertension-resistant (R) and hypertension-sensitive (S) strains of rats. Investigation of the effects of chlorothiazide on blood pressure, 24-hour urinary 24Na and aldosterone excretion, and plasma renin activity (PRA) produced the following observations: (1) Chlorothiazide failed to prevent the development of salt hypertension in S rats. (2) After 12 weeks, S rats on high salt puls chlorothiazide exhibited a rapid fall in blood pressure to levels indistinguishable from those of S rats on low salt. (3) Chlorothiazide significantly increased urinary 24Na excretion only in S rats on high salt (P less than 0.01). (4) Chlorothiazide significantly increased PRA and urinary aldosterone excretion in both strains on low or high salt diets (P less than 0.001). (5) Morbidity and mortality of salt hypertension were alleviated by chlorothiazide treatment. The unique aspect of this study is the finding that chlorothiazide did not abolish the hypertensiogenic action of salt in S rats.
Assuntos
Clorotiazida/farmacologia , Hipertensão/induzido quimicamente , Cloreto de Sódio/efeitos adversos , Aldosterona/urina , Animais , Pressão Sanguínea/efeitos dos fármacos , Clorotiazida/administração & dosagem , Masculino , Natriurese/efeitos dos fármacos , Ratos , Renina/sangue , Cloreto de Sódio/administração & dosagemRESUMO
A reciprocal relationship between steroid 18- and 11beta-hydroxylase activities in the salt susceptible (S) and the salt resistant (R) strains of rats was previously shown to be controlled by a single genetic locus with two alleles and inheritance by co-dominance (Rapp, J. P., and Dahl, L. K. (1972), Endocrinology 90, 1435). The strain specific steroidogenic patterns, characterized by the relative magnitudes of 18- and 11beta-hydroxylase activities, were found to be determined by adrenal mitochondrial cytochrome P-450 particles. Carbon monoxide inhibition of 18- and 11beta-hydroxylation of deoxycorticosterone in these strains showed that the CO/O2 ratio causing 50% inhibition (i.e., Warburg's partition constant, K) was identical for 18- and 11beta-hydroxylation within a strain, but different for both 18- and 11 beta hydroxylation between strains. (K values were: S rats, 18-hydroxylation = 11.4 +/- 1.4; S rats, 11beta-hydroxylation = 11.0 +/- 1.2; R rats, 18-hydroxylation = 56.4 +/- 13.7; R rats, 11beta-hydroxylation = 46.7 +/- 11.7). This between-strain difference was unique for 18- and 11beta-hydroxylation; i.e., it was not seen with cholesterol side-chain cleavage or 21-hydroxylation. Moreover, the strain-specific K values for 18- and 11beta-hydroxylase and the strain-specific steroidogenic patterns due to the relative magnitudes of 18- and 11beta-hydroxylase activities segregated together in an F2 population. These data strongly suggest the same cytochrome P-450 is involved in both 18- and 11beta-hydroxylation and that this cytochrome is mutated between S and R rats. K values for the reaction corticosterone leads to 18-hydroxycorticosterone were different between S and R strains, indicating that the mutant cytochrome was also involved in this hydroxylation, but K values for the conversion corticosterone leads to aldosterone were not different between strains. This was interpreted to mean that each step in the sequence corticosterone leads to 18-hydroxycorticosterone leads to aldosterone was mediated by a different cytochrome, the K value for the second step being the lower and dominating the overall reaction. It was speculated that the second step could be a second hydroxylation at position 18 to yield 18,18-dihydroxycorticosterone which could be unstable and decompose into aldosterone and water.
Assuntos
Glândulas Suprarrenais/enzimologia , Sistema Enzimático do Citocromo P-450/metabolismo , Mitocôndrias/enzimologia , Mutação , Esteroide Hidroxilases/metabolismo , Aerobiose , Anaerobiose , Animais , Fracionamento Celular , Sistema Enzimático do Citocromo P-450/isolamento & purificação , Feminino , Cinética , Matemática , RatosRESUMO
In a genetically hypertension-prone (S) strain of rats it was observed previously that males generally developed hypertension more rapidly on a high salt diet than did females although final pressure ultimately were similar in both sexes. A genetic study had shown that there was no sex-linkage involved in setting blood pressure levels, so it was thought that the gonads might be involved. In the present work, castration of males had no effect on blood pressure but in the females it caused a rise in pressure that could not be distinguished from that in males, both on a high and low salt diet. Castration resulted in greater growth in females than in controls, whereas it had the opposite effect in males. It was speculated that these changes were due to influences on pituitary growth hormone with castration increasing the net output of growth hormone (or enhancing receptor sensitivity to it) in the female and the opposite in the male. From the work of others, there are some data compatible with such an interpretation. Experimentally, growth hormone will induce hypertension in rats. Therefore, it is conceivable that growth hormone is involved in the increment in hypertension observed in these castrate females. Because the effect on blood pressure was observed in castrate females on both high and low NaCl diets, it was considered unlikely that the blood pressure effect was simply due to increased NaCl intake in the food associated with greater growth. It was suggested that this rise in blood pressure with cessation of ovarian function might bear on the unsettled question of "menopausal" hypertension in women: in the genetically susceptible individual an increase in growth hormone associated with declining ovarian funtion in the menopause could provide the stimulus for the appearance of hypertension some years earlier than would otherwise have been the case.
Assuntos
Hormônio do Crescimento/fisiologia , Hipertensão/etiologia , Ovário/fisiologia , Animais , Peso Corporal , Castração , Dieta/efeitos adversos , Feminino , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Ratos , Fatores Sexuais , Cloreto de Sódio/efeitos adversos , Fatores de TempoRESUMO
Rats with a genetic susceptibility to experimental hypertension were exposed daily for 13 weeks to a conflict situation that resulted in food deprivation and the application of electric shock. Other subjects were either food deprived, shocked, both food deprived and shocked but without conflict, or not experimentally manipulated (control). Despite weekly fluctuations, a pattern emerged wherein subjects exposed to conflict usually exhibited the highest systolic blood pressures followed in order by subjects exposed to food deprivation and shock without conflict, rats food deprived, rats exposed to shock, and control subjects. Following this 13 week period, some of the rats in each group were allowed a 13 week stress-free-recovery period while the rest of the subjects were treated as before. During the recovery period most subjects' blood pressure returned to control levels. However, there was some indication in a few rats that elevations could persist for extended periods after the aversive treatment had been terminated. There is probably a genetic component involved in the reaction to stress that promotes the development of hypertension, just as there is to other hypertensinogenic stimuli.
Assuntos
Pressão Sanguínea , Conflito Psicológico , Hipertensão/genética , Estresse Psicológico , Animais , Peso Corporal , Condicionamento Operante , Eletrochoque , Comportamento Alimentar , Privação de Alimentos , Humanos , Masculino , Atividade Motora , Punição , Ratos , Fatores de Tempo , Vocalização AnimalRESUMO
The genotype of homograft kidneys plays the primary role in determining chronic blood pressure levels in two strains of rats with opposite genetically controlled propensities for hyptertension. In hypertensive rats from the hypertension-prone (S) strain, a renal homograft from the same strain resulted in a slight rise in blood pressure to a level that was equivalent to that in appropriate uninephrectomized S controls. In contrast, a renal homograft from the hypertension-resistant (R) strain led to a sharp fall in blood pressure in hypertensive S recipients. Opposite results were found when the host came from the R strain: R homografts maintained the same low pressure as that seen in controls, whereas S homografts resulted in hypertension. We concluded that genetically controlled factors operating through the kidney can chronically modify the blood pressure up or down. The central role of the kidney in hypertension is thus further documented.
Assuntos
Pressão Sanguínea , Genótipo , Hipertensão/genética , Transplante de Rim , Animais , Nitrogênio da Ureia Sanguínea , Dieta , Ratos , Ratos Endogâmicos , Cloreto de Sódio , Fatores de Tempo , Transplante HomólogoAssuntos
Coloides/análise , Hipertensão/genética , Hipófise/embriologia , Proteínas/análise , Cloreto de Sódio/efeitos adversos , Análise de Variância , Animais , Eletroforese , Histocitoquímica , Hipertensão/induzido quimicamente , Hormônios Estimuladores de Melanócitos/análise , Hormônios Estimuladores de Melanócitos/fisiologia , Natriurese , Hipófise/análise , Hipófise/anatomia & histologia , RatosAssuntos
Pressão Sanguínea , Hipertensão/genética , Transplante de Rim , Injúria Renal Aguda/etiologia , Animais , Nitrogênio da Ureia Sanguínea , Dieta , Dieta Hipossódica/efeitos adversos , Rim/fisiologia , Ratos , Ratos Endogâmicos , Cloreto de Sódio/administração & dosagem , Fatores de Tempo , Transplante HomólogoAssuntos
Diurese/efeitos dos fármacos , Hipertensão/genética , Natriurese/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Animais , Dieta Hipossódica , Hipertensão/fisiopatologia , Soluções Isotônicas , Rim/fisiopatologia , Capacidade de Concentração Renal , Túbulos Renais Proximais/fisiopatologia , Concentração Osmolar , Ratos , Ratos Endogâmicos , Especificidade da EspécieAssuntos
Angiotensina II , Hipertensão/genética , Rim/metabolismo , Renina/metabolismo , Angiotensina II/análise , Animais , Pressão Sanguínea , Hipertensão/etiologia , Rim/análise , Rim/efeitos dos fármacos , Rim/fisiopatologia , Ratos , Renina/análise , Cloreto de Sódio/farmacologia , Estatística como AssuntoAssuntos
Pressão Sanguínea , Genes , Mineralocorticoides/metabolismo , Glândulas Suprarrenais/metabolismo , Alelos , Animais , Pressão Sanguínea/efeitos dos fármacos , Isótopos de Carbono , Gatos , Corticosterona/metabolismo , Cruzamentos Genéticos , Técnicas de Cultura , Desoxicorticosterona/metabolismo , Feminino , Hidrocortisona/metabolismo , Hidrocortisona/farmacologia , Hipertensão/epidemiologia , Masculino , Fenótipo , Seleção Genética , Fatores Sexuais , Cloreto de Sódio/farmacologiaAssuntos
Aldosterona/sangue , Cloreto de Sódio/farmacologia , Glândulas Suprarrenais/irrigação sanguínea , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Aldosterona/biossíntese , Análise de Variância , Animais , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea/efeitos dos fármacos , Corticosterona/sangue , Corticosterona/metabolismo , Desoxicorticosterona/sangue , Dieta , Feminino , Tamanho do Órgão , Ratos , Fluxo Sanguíneo RegionalRESUMO
Among genetically hypertension-prone rats, dietary sodium (chloride) was demonstrably hypertensinogenic and potassium (chloride) antihypertensinogenic. On diets containing the same NaCl but different KCl concentrations, mean blood pressure was greater in rats receiving less dietary potassium, i.e., diets with a higher Na/K molar ratio. On diets with different absolute concentrations of NaCl and KCl, but the same Na/K molar ratios, rats on the higher absolute NaCl intakes had the higher blood pressures. On diets with different absolute concentrations of NaCl and KCl, and different Na/K molar ratios, a group on a lower absolute NaCl intake but with a higher Na/K ratio could have more hypertension than a group on a higher absolute NaCl intake but with a lower Na/K ratio. At equivalent molar ratios, the respective effects of these two ions on blood pressure were dominated by that of sodium. It was concluded that the dietary Na/K molar ratio can be an important determinant for the severity, or even development, of salt-induced hypertension. The mechanism of the moderating effect of potassium on sodium-induced hypertension was unclear.