RESUMO
We have previously shown that chronic treatment with angiotensin-converting enzyme inhibition (ACEI) did not reverse hypertrophy of the renal arterial wall in spontaneously hypertensive rats (SHR). In this study we determined the effects of perindopril on the functional properties of the renal vasculature in vivo and on its resistance to flow at maximal dilatation in vitro, a measure of vessel lumen diameter. Two groups of SHR were studied: untreated or treated with perindopril (3 mg/kg per day) in their drinking water from 4 weeks of age. At 10 weeks, (1) vessel lumen characteristics were assessed using a maximally dilated in vitro isolated kidney perfusion and (2) the renal vasoconstrictor responses to bolus doses of vasoactive agents (angiotensin II and phenylephrine) administered into the renal artery were measured in vivo (anesthetized rats). Mean arterial pressure was significantly lower in conscious SHR treated with perindopril (132+/-2 versus 97+/-2 mm Hg, P<.001). In vitro, the pressure-flow relationship and the pressure-glomerular filtration rate relationship were both shifted significantly to the left (P<.001). The perindopril-treated kidneys began filtering at a significantly lower threshold perfusion pressure than nontreated controls (P<.001). In vivo, renal vasoconstrictor responses to increasing doses of both vasoconstrictor agents were significantly less marked in the perindopril-treated SHR than in untreated SHR (P<.05). Thus, chronic ACEI increased average renal vessel lumen diameter in SHR, predominantly in preglomerular vessels, and reduced renal vasoconstrictor responsiveness in vivo, findings compatible with remodeling of the preglomerular vasculature around a greater lumen.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Hipertensão/tratamento farmacológico , Indóis/farmacologia , Rim/irrigação sanguínea , Artéria Renal/efeitos dos fármacos , Vasoconstritores/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Perindopril , Ratos , Ratos Endogâmicos SHRRESUMO
1. The transplacental transfers of three drugs (enalapril, captopril and losartan) which block the renin angiotensin system and have different lipophilicities were studied in chronically catheterized foetal sheep (125-139 days gestation). 2. The ability of the foeto-placental unit to convert enalapril to enalaprilat was studied in two chronically catheterized foetuses. Enalapril (3 mg kg-1, 7.9 mumol kg-1) given i.v. to the foetuses abolished the foetal pressor response to 5 micrograms angiotensin I (AI) in one foetus and attenuated the pressor response in the other. 3. Enalapril (100 mg, 5.7 mumol kg-1) given i.v. to the ewe (n = 5) abolished the maternal pressor response to 2.5 micrograms AI (n = 1) and attenuated the maternal pressor response to 5 micrograms AI (n = 5, P < 0.001). The foetal pressor response to 5 micrograms AI (n = 2) and 10 micrograms AI (n = 3) did not change. The maternal and foetal pressor responses to angiotensin II (AII; n = 5) did not change. 4. Foetal pressor responses to 5 micrograms AI (n = 1) and 10 micrograms AI (n = 2) were attenuated within 11 min of their mothers (n = 3) being given i.v. captopril (15 mg, 1.5 mumol kg-1). Foetal pressor responses to 5 micrograms AII (n = 1) and to 10 micrograms AII (n = 2) did not change. 5. Losartan (100 mg, kg-1, 21.7 mumol kg-1) given i.v. to the foetus (n = 9) attenuated the foetal pressor response to 5 micrograms AII (P < 0.001) but the maternal pressor response to 5 micrograms AII did not change. 6. Losartan (100 mg, 21.7 MICROmol kg-1) given i.v. to the ewe (n = 5) attenuated the maternal pressor response to 5 microg AII (P <0.002) but the foetal pressor response to 5 microg AII did not change.7. It is concluded that the foeto-placental unit of the sheep can metabolize enalapril to enalaprilat.Captopril readily crosses the sheep placenta but enalapril and losartan do not. Thus, the transplacental transfer of these drugs does not parallel their lipid solubilities. Furthermore the results show that AT1 receptors are important in mediating the vasoconstrictor effects of AII in the foetus.
Assuntos
Compostos de Bifenilo/farmacocinética , Captopril/farmacocinética , Enalapril/farmacocinética , Imidazóis/farmacocinética , Placenta/metabolismo , Tetrazóis/farmacocinética , Angiotensina I/farmacologia , Antagonistas de Receptores de Angiotensina , Animais , Transporte Biológico/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Feminino , Feto/efeitos dos fármacos , Feto/metabolismo , Injeções Intravenosas , Losartan , Placenta/efeitos dos fármacos , OvinosRESUMO
To test the validity of transit-time ultrasound flowmetry for chronic measurement of renal blood flow in dogs, we compared this method with the renal clearance of para-aminohippuric acid (CPAH) (corrected for hematocrit), and with direct volumetric measurements. When flow-probes were implanted without silastic sheeting to stabilize the implant, there was significant disparity between the (within-dog) mean levels of renal blood flow estimated by flow-probe and CPAH. In contrast, when the flow-probe implants were stabilized with silicone sheeting, there was close agreement in each dog between the flow rates measured by the two methods. When flow-probes were calibrated volumetrically in situ, there was a close linear relationship between flow derived from the flow-probe and that measured volumetrically (r = 0.98 +/- 0.02). We conclude that valid, chronic measurement of renal blood flow in dogs can be achieved using transit-time ultrasound flowmetry, provided the implant is stabilized with silicone sheeting.
Assuntos
Rim/irrigação sanguínea , Circulação Renal/fisiologia , Ultrassonografia/métodos , Animais , Velocidade do Fluxo Sanguíneo , Cães , Testes de Função Renal/métodos , Masculino , Próteses e Implantes , Reprodutibilidade dos Testes , Reologia/métodos , Elastômeros de Silicone , Ácido p-Aminoipúrico/farmacocinéticaRESUMO
A model training protocol for case management of child sexual abuse cases, with a concomitant competency-based evaluation of these skills, is presented. Findings suggest that relative to skills in problem identification, child protective service workers need training in formulating goals and objectives and negotiating contracts with sexually abusive families.
Assuntos
Abuso Sexual na Infância/terapia , Competência Profissional , Serviço Social/educação , Criança , Abuso Sexual na Infância/prevenção & controle , Proteção da Criança , Currículo , HumanosRESUMO
This paper reviews the research that reports (a) some of the physical and social considerations in treating the obese, (b) characteristics that identify overeaters and some implications for treatment, and (c) treatment settings and personnel who treat the obese. It then examines three major treatment approaches utilized by social workers and other health care professionals and reports findings on the effectiveness of each. Finally, it describes one weight reduction treatment program in which social work intervention is viewed as a central and vital component. In conclusion, issues for the practitioner's further consideration regarding intervention with this population are presented.
Assuntos
Obesidade/terapia , Meio Social , Adolescente , Adulto , Assistência Ambulatorial , Terapia Comportamental , Sinais (Psicologia) , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/psicologia , Esforço Físico , Pesquisa , Grupos de Autoajuda , Serviço Social em PsiquiatriaRESUMO
The effects of indomethacin (10 mg/kg i.v. to the ewe and 12 mg/kg i.v. to the fetus) were examined in 8 chronically catheterized fetal sheep (117-138 days gestation). These doses suppressed fetal 6-keto-prostaglandin F1 alpha and thromboxane B2 levels. Fetal arterial PO2 increased (P < 0.01); PCO2 (P < 0.001) and pH fell (P < 0.001) and arterial pressure did not change. Placental blood flow increased in 4 of the 5 fetuses in which blood flows were measured. Lung liquid flow rate fell (P < 0.001). Fetal renal blood flow did not change but its distribution did, i.e. flow to the inner part of the renal cortex decreased (P < 0.05). Urine flow rates did not change but there was a natriuresis (P < 0.02), kaliuresis (P < 0.02) and chloriuresis (P < 0.02). Urinary osmolality rose (P < 0.001) and free water clearance fell (P = 0.004). It is concluded that when indomethacin is administered to both ewe and fetus, the resulting fall in prostaglandin I2 and thromboxane A2 levels causes marked changes in fetal blood gas status, renal function and lung liquid production. These effects are more profound than those seen when indomethacin is given only to the fetus. They do not however, explain the reason why clinical use of indomethacin is associated with a reversible oligohydramnios.
Assuntos
Água Extravascular Pulmonar/efeitos dos fármacos , Sangue Fetal/efeitos dos fármacos , Feto/efeitos dos fármacos , Indometacina/farmacologia , Rim/efeitos dos fármacos , Placenta/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Dióxido de Carbono/sangue , Eletrólitos/sangue , Feminino , Sangue Fetal/química , Feto/irrigação sanguínea , Feto/fisiologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca Fetal/efeitos dos fármacos , Rim/embriologia , Oxigênio/sangue , Placenta/irrigação sanguínea , Gravidez , Fluxo Sanguíneo Regional/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , OvinosRESUMO
1. Angiotensin II (AII) was infused I.V. into seven chronically catheterized fetal sheep (gestational age, 120-136 days). The effects of short-term infusions of 6 and 12 micrograms kg-1 h-1 for 1.5 h were compared with the effects of infusing 6 micrograms kg-1 h-1 for 3 or 5 days (long-term infusion). AII produced an immediate rise in fetal arterial blood pressure (P < 0.025). When infused for 3 or 5 days, 6 micrograms kg-1 h-1 AII caused a greater increase in arterial blood pressure (P < 0.05). 2. Infusions of 6 micrograms kg-1 h-1 AII for 1.5 h had no effect on fetal placental blood flow or on flow to the fetal membranes, but after AII infusion for 3 or 5 days both flows were reduced (P < 0.01 and P < 0.005, respectively). Fetal blood gas status and pH were maintained. The only change in fetal renal function observed with short-term infusions of AII was a rise in sodium excretion when 12 micrograms kg-1 h-1 AII was given (P < 0.05). Infusion of 6 micrograms kg-1 h-1 for 3 or 5 days also caused a rise in sodium excretion (P < 0.025) because total and proximal fractional sodium reabsorptions were depressed (P < 0.01). Infusions of AII had no effects on the volume of lung liquid produced or on its composition. 3. Administration of indomethacin to the ewe (10 mg kg-1) and to the fetus (12 mg kg-1), during the infusion of AII, caused a rise in maternal arterial pressure (P < 0.01) but no change in fetal arterial pressure. 4. After indomethacin, umbilicoplacental blood flow rose (P < 0.05), as did fetal arterial PO2 (P < 0.05). Fetal arterial PCO2, pH and bicarbonate levels fell (P < 0.01). Glomerular filtration rate (GFR) rose (P < 0.01); there was a natriuresis (P < 0.01), chloriuresis (P < 0.01) and a kaliuresis (P < 0.05) but urine flow rate did not change. Lung liquid flow fell (P < 0.01). 5. It is concluded that in the fetus, long-term infusions of AII at a constant dose rate cause a progressive rise in arterial pressure. In addition, effects of AII on placental blood flow and on renal function develop. Thus, short-term infusions of AII cannot be used to predict the renal and cardiovascular effects of sustained high levels of this peptide in the fetus.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Angiotensina II/farmacologia , Feto/efeitos dos fármacos , Indometacina/farmacologia , Prenhez/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Feminino , Infusões Intravenosas , Placenta/irrigação sanguínea , Gravidez , Fluxo Sanguíneo Regional/efeitos dos fármacos , Ovinos/embriologiaRESUMO
1. The angiotensin type 1 (AT1) receptor antagonist, losartan (10 mg/kg) was infused intravenously into nine chronically catheterized fetal sheep (125-132 days gestation). Losartan reduced the fetal systolic (P <0.01) and diastolic (P <0.01) pressor response to 5 microg angiotensin II (AngII) i.v. from 27.4 +/- 1.5 to 7.4+/-0.9 and from 17.5 +/- 1.3 to 5.4 +/- 0.6 mmHg, respectively, after 1 h and to 6.1 +/- 0.5 and 4.4 +/- 0.5 mmHg, respectively, after 2 h. Maternal pressor responses to 5 microg AngII i.v. were unchanged. Fetal mean arterial pressure decreased (P <0.05) after losartan administration, but fetal heart rate did not change. 2. Fetal haematocrit increased (P <0.05), fetal PO2 decreased (P <0.01), PCO2 did not change and pH decreased (P <0.01), as did plasma bicarbonate levels (P <0.01) following administration of losartan. Thus, losartan induced a fetal metabolic acidosis. 3. Fetal placental blood flow did not change following administration of losartan. In the fetal kidney, losartan caused a decrease in vascular resistance (P <0.01) and an increase in blood flow (P <0.05). Glomerular filtration rate decreased (P <0.05); thus, filtration fraction decreased (P <0.01). There was no change in the fractional reabsorption of sodium and glomerulotubular balance was maintained. Free water clearance decreased (P <0.01) and became negative. Urine flow decreased (P <0.01), the excretion rates of sodium, potassium and chloride did not change, but the urinary sodium: potassium ratio decreased (P <0.05). There was a decrease in lung liquid flow (P <0.05) following losartan. 4. It is concluded that the fetal renin-angiotensin system (RAS) is important in the maintenance of fetal arterial pressure, the regulation of fetal renal blood flow and is essential in the maintenance of fetal glomerular function. Further, these actions of AngII are mediated via functional AT1 receptors. These effects of losartan on the fetal cardiovascular system, renal blood flow and function are similar to those observed following captopril administration. Thus, the effects of angiotensin converting enzyme (ACE) inhibition in the foetus are due to the blockade of the fetal RAS and are independent of any direct effects on bradykinin or prostaglandin levels.
Assuntos
Anti-Hipertensivos/farmacologia , Compostos de Bifenilo/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Feto/efeitos dos fármacos , Imidazóis/farmacologia , Circulação Renal/efeitos dos fármacos , Tetrazóis/farmacologia , Animais , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/sangue , Compostos de Bifenilo/efeitos adversos , Compostos de Bifenilo/sangue , Líquidos Corporais , Feminino , Imidazóis/efeitos adversos , Imidazóis/sangue , Losartan , Pulmão/efeitos dos fármacos , Gravidez , Ovinos , Tetrazóis/efeitos adversos , Tetrazóis/sangue , Urodinâmica/efeitos dos fármacosRESUMO
Careful needs assessment is a prerequisite to addressing issues of health care program effectiveness and program planning from a population-based perspective. Home care program evaluation literature is lacking in examples of strategies for such assessment. A nurse-screening of admissions was conducted at an acute care general hospital to estimate need for hospital-based home care (HBHC) services among the 2,613 patients discharged from medical and surgical services over a 5-month period. After careful delineation of inclusion and exclusion criteria for identifying HBHC patients and participant-observer training, the nurse's judgments on patient appropriateness for HBHC care were shown to agree reliably with those of the HBHC staff (k = + .45). In the study hospital under current conditions, an estimated 64% of discharged patients appropriate for home care do not receive these services. A comparison of the incidence according to service of HBHC-appropriate patients and patient-referral rates to HBHC suggests that one service over-refers (neurology), but most under-refer. Screening nurse salary expenditures constitute the major costs of this approach to home care needs assessment, which is recommended only for addressing major, infrequent programmatic policy issues.
Assuntos
Necessidades e Demandas de Serviços de Saúde , Pesquisa sobre Serviços de Saúde , Serviços de Assistência Domiciliar/organização & administração , Hospitais Gerais , Adolescente , Adulto , Idoso , Feminino , Hospitais de Veteranos , Humanos , Masculino , Pessoa de Meia-Idade , WashingtonRESUMO
Low birth weight has been associated with elevated arterial pressure in later life but mechanisms are unknown. Our aim was to determine the effects of low birth weight resulting from intrauterine growth restriction (IUGR) on fetal and postnatal arterial pressures and the potential roles of circulating cortisol and renin. We induced IUGR by umbilico-placental embolization (UPE) in fetal sheep from 120 d of gestation until birth (approximately 147 d); postnatal lambs (8 IUGR, 8 controls) were studied for 8 wk. Fetal and postnatal arterial pressures were measured and blood samples taken for measurement of gas tensions, cortisol concentrations and renin activity. In IUGR fetuses, mean arterial pressure (MAP) initially increased with UPE, but near term was not different to values in controls. IUGR lambs weighed 33% less than controls at birth and remained lighter than controls during the 8 postnatal weeks; their growth pattern was different to that of controls. IUGR lambs had lower MAP than controls, and this relative hypotension (-4 mm Hg) persisted throughout the 8 postnatal weeks. Covariate analysis showed that the relative hypotension of IUGR lambs could have resulted from their smaller size. Plasma cortisol concentrations were not different between IUGR and control animals before or after birth. Plasma renin activity was not different in postnatal IUGR lambs compared with controls. Thus, postnatal cortisol and renin levels were not consistent with the development of hypotension or hypertension. We conclude that late gestational IUGR in sheep leads to relative hypotension in the early postnatal period, probably a result of reduced body size.
Assuntos
Retardo do Crescimento Fetal/complicações , Transtornos do Crescimento/etiologia , Hipotensão/etiologia , Insuficiência Placentária/complicações , Animais , Peso ao Nascer , Pressão Sanguínea , Peso Corporal , Feminino , Sangue Fetal/química , Idade Gestacional , Transtornos do Crescimento/sangue , Transtornos do Crescimento/patologia , Frequência Cardíaca , Hidrocortisona/sangue , Concentração de Íons de Hidrogênio , Hipotensão/sangue , Rim/patologia , Masculino , Miocárdio/patologia , Tamanho do Órgão , Gravidez , Renina/sangue , OvinosRESUMO
Angiotensin II was infused at 0.5 ng/kg/min either directly into the left renal artery (n = 5) or intravenously (n = 4) for 28 days in conscious dogs. Renal artery infusion of angiotensin II had no significant effect on mean arterial pressure after 1 and 24 h, but pressure had increased by 12 +/- 2, 12 +/- 4, 8 +/- 3 and 13 +/- 3 mmHg on days 7, 14, 21 and 28, respectively, during infusion. Renal blood flow decreased significantly at 24 hours (p = 0.02) but was not significantly reduced subsequently. Over days 7-28, central venous pressure and haematocrit rose significantly but body weight did not change significantly. During intravenous infusion of angiotensin II, arterial pressure increased (5 +/- 4, 7 +/- 5 and 5 +/- 3 mmHg on days 7, 14 and 21, respectively), body weight rose and haematocrit fell significantly, but central venous pressure did not change. Thus, angiotensin II infused into the renal artery, at a dose which had no initial pressor effect, produced chronic, stable hypertension, with equivocal evidence of renal fluid retention. We conclude that elevated levels of angiotensin II in the kidney alone can cause chronic hypertension.
Assuntos
Angiotensina II/toxicidade , Hipertensão Renal/induzido quimicamente , Circulação Renal/efeitos dos fármacos , Vasoconstritores/toxicidade , Animais , Doença Crônica , Cães , Relação Dose-Resposta a Droga , Infusões Intra-Arteriais , Infusões Intravenosas , Projetos Piloto , Artéria Renal , Cloreto de Sódio/metabolismo , Resistência Vascular/efeitos dos fármacos , Água/metabolismoRESUMO
1. To determine whether chronic angiotensin II (AngII) infusion into the renal artery, at a dose which increases systemic arterial pressure, reduces glomerular filtration rate (GFR) and renal blood flow, AngII was infused at 0.5 ng/kg per min into the renal artery or intravenously in chronically instrumented dogs for 1 month. 2. Mean arterial pressure (MAP) rose significantly (P < 0.05) during the infusion of AngII into the renal artery (+7 +/- 2 mmHg on days 26-30). There were no significant changes in GFR or renal blood flow. When the same dose of AngII was infused intravenously, MAP did not change significantly (-2 +/- 2 mmHg) and there were no significant changes in GFR or in renal blood flow. 3. We conclude that AngII infused into the renal artery for 1 month, at a dose which was initially subpressor, causes a rise in arterial pressure that is not associated with impairment of renal function.
Assuntos
Angiotensina II/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Rim/efeitos dos fármacos , Animais , Creatinina/sangue , Cães , Relação Dose-Resposta a Droga , Esquema de Medicação , Taxa de Filtração Glomerular/efeitos dos fármacos , Infusões Intra-Arteriais , Infusões Intravenosas , Rim/irrigação sanguínea , Rim/fisiologia , Masculino , Artéria RenalRESUMO
Chronic intrarenal infusion of angiotensin II (0.5 ng.kg-1.min-1) in dogs increases arterial pressure. In the present study we determined whether this was associated with changes in cardiac output or in total peripheral resistance. Mean arterial pressure did not change initially but was significantly increased over days 14-28 of the infusion period (+6 +/- 2 mmHg), as was total peripheral resistance (+4 +/- 2 mmHg.min.l-1). Neither cardiac output, renal blood flow, nor glomerular filtration rate was significantly changed over this period. To determine the influence of the autonomic nervous system on the developing hypertension, periodic acute autonomic ganglion blockade was performed. Before angiotensin II infusion ganglion blockade reduced total peripheral resistance and increased cardiac output, and this effect was similar across the 4 wk of angiotensin II infusion. Systemic hemodynamics were not affected by intravenous angiotensin II infusion (0.5 ng.kg-1.min-1). Thus intrarenal infusion of low-dose angiotensin II produced a chronic increase in arterial pressure due to an action within the kidney. The hypertension was associated with increased total peripheral resistance but not with marked changes in cardiac output or renal function or in the influence of the autonomic nervous system on systemic hemodynamics.
Assuntos
Angiotensina II/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipertensão/fisiopatologia , Rim/fisiologia , Artéria Renal/fisiologia , Angiotensina II/administração & dosagem , Animais , Débito Cardíaco/efeitos dos fármacos , Cães , Gânglios Autônomos/efeitos dos fármacos , Gânglios Autônomos/fisiologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Infusões Intra-Arteriais , Rim/efeitos dos fármacos , Rim/inervação , Masculino , Fluxo Sanguíneo Regional/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , Circulação Renal/fisiologia , Fatores de Tempo , Resistência Vascular/efeitos dos fármacosRESUMO
1. We tested whether chronic intrarenal angiotensin II (AngII) infusion altered renal vascular responsiveness to vasoactive agents, which would provide evidence of vascular structural changes. 2. The renal blood flow (RBF) responses to renal arterial administration of bolus doses of acetylcholine, glyceryl trinitrate, AngII and noradrenaline were measured before commencement of and 1 day after cessation of 28 days intrarenal AngII infusion (0.5 ng/kg per min) in chronically instrumented conscious dogs. 3. The RBF responses to these vasoactive agents were unaltered by chronic intrarenal AngII infusion in conscious dogs. 4. These functional studies provide no evidence for renal vascular hypertrophy in response to chronic intrarenal AngII infusion in conscious dogs.
Assuntos
Angiotensina II/farmacologia , Circulação Renal/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Acetilcolina/farmacologia , Angiotensina II/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Cães , Injeções , Rim , Nitroglicerina/farmacologia , Norepinefrina/farmacologia , Resistência Vascular/efeitos dos fármacosRESUMO
The effects on the renal vasculature and on arterial blood pressure of chronic infusion of low doses of angiotensin II (Ang II) into the renal artery were studied. Sprague Dawley rats were infused continuously with Ang II (0.5, 1.5, or 4.5 ng. kg(-1). min(-1)) or vehicle into the right renal artery (contralateral nephrectomy). Intrarenal Ang II infusion for 25 days produced dose-dependent rises (P:<0.001) in awake mean arterial pressure (111+/-1, 119+/-5, and 130+/-3 mm Hg in rats receiving 0.5, 1.5, and 4.5 ng. kg(-1). min(-1) Ang II, respectively) compared with 105+/-1 mm Hg (vehicle). Renal vessel lumen characteristics were assessed with an established, maximally dilated, isosmotic perfused kidney preparation. This revealed a small dose-dependent right shift in the pressure-flow relation (P=0.05), as well as a dose-dependent right shift and a dose-dependent reduction in the slope of the pressure-glomerular filtration rate relation (P=0.04 and 0.03, respectively). The effects of Ang II infusion on arterial pressure were not affected by the timing of the contralateral nephrectomy but were reduced when the contralateral kidney remained in situ. Acute losartan administration (10 mg/kg IV bolus) produced similar effects on arterial pressure in rats infused with vehicle or Ang II (4.5 ng. kg(-1). min(-1)) for 14 days, P=0.89), indicating the lack of systemic spillover of Ang II. Intraperitoneal Ang II (0.5, 1.5, or 4.5 ng. kg(-1). min(-1) for 25 days) had no effect on arterial pressure. Thus, chronic intrarenal infusion of low doses of Ang II resulted in changes in the renal vasculature compatible with dose-related structural reductions in the lumen diameter of preglomerular vessels and produced dose-related increases in arterial pressure.
Assuntos
Angiotensina II/administração & dosagem , Angiotensina II/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/induzido quimicamente , Rim/efeitos dos fármacos , Angiotensina II/antagonistas & inibidores , Animais , Anti-Hipertensivos/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Taxa de Filtração Glomerular/efeitos dos fármacos , Infusões Intra-Arteriais , Losartan/farmacologia , Masculino , Nefrectomia , Ratos , Ratos Sprague-Dawley , Artéria Renal/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacosRESUMO
Experimental narrowing of the main renal artery to produce hypertension increases the aorta-glomerular capillary pressure difference and vascular resistance. This article examines the hypothesis that hypertension also may be caused by structural changes that narrow intrarenal blood vessels, similarly increasing preglomerular vascular resistance and the aortic-glomerular capillary pressure gradient. There is evidence of both wall hypertrophy and lumen narrowing of the preglomerular arteries in spontaneously hypertensive rats, with increased preglomerular resistance and aortic-glomerular capillary pressure difference. We have also attempted to induce structural changes in renal-preglomerular vessels experimentally by infusing angiotensin II at low doses (0.5 to 4.5 ng/kg per minute) into the renal artery of Sprague-Dawley rats and greyhound dogs for up to 4 weeks. This angiotensin II infusion produced apparent dose-related effects on preglomerular vessel structure and hypertension. The possibility that hypertension may be induced by structural changes in preglomerular resistance vessel walls, by simulation of the hemodynamic effects of main renal artery stenosis, deserves further investigation.
Assuntos
Hipertensão Renovascular/patologia , Rim/irrigação sanguínea , Rim/patologia , Angiotensina II/administração & dosagem , Animais , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Renovascular/induzido quimicamente , Rim/efeitos dos fármacos , Nefrectomia , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Obstrução da Artéria Renal/patologia , Resistência Vascular/efeitos dos fármacosRESUMO
We tested for sex-related differences in the pressure diuresis/natriuresis relationships in anaesthetized, renally denervated rabbits, using an extracorporeal circuit to perfuse the left kidney with the rabbit's own blood, through a series of step-wise increases in renal artery pressure (RAP) (from 65 to 130 mmHg). Urine flow, sodium excretion, and the fractional excretions of sodium and urine increased with increasing RAP, and were greater in male than in female rabbits at all levels of RAP-tested. However, these apparent sex-related differences in the acute pressure diuresis/natriuresis relationships were not reflected in alterations in chronic regulation of mean arterial pressure (MAP). Thus, in rabbits on a normal salt diet (0.85 g day(-1)), resting conscious MAP was significantly greater in males (87 +/- 3 mmHg) compared with females (77+/-1 mmHg). Chronically increasing daily salt intake to 4.98 g day(-1) for 28 days had no significant effect on resting conscious MAP in either sex. Thus, although our observations indicate sex differences, at least under the present experimental conditions, in the factors regulating extracellular fluid volume, these do not appear to have a major impact in setting the level of MAP in the long term.