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Peptide Hormones and the Regulation of Sodium Excretion
RENAL PHYSIOLOGY, RENAL FAILURE AND HYPERTENSION
ritis. To define the regulation of IL-1 synthesis human Northern blot analyses were performed using specific probes for monocytic IL-1 a and (3 mRNA. Proliferating MC expressed mRNA for both IL-1 a and (3, whereas nonproliferating MC contained no detectable IL-1 mRNA. Synchronized MC expressed IL-1 a and (3 mRNA within 2 h of stimulation with serum. This serum effect could be reproduced with plateletderived growth factor and epidermal growth factor. Immune precipitations of ' 5 S-methionine-labeled cells indicate that the mesangial IL-1 is synthesized as a 33-kD precursor protein with a pl of 7.2. Extracellular mesangial IL-1 has a pl of 7.0 and molecular weight of 17 kD, consistent with its identification as IL-1 (3. Cellular proliferation in glomerular disease may be driven in part by peptide growth factor-mediated induction of mesangial IL-1 gene expression and protein synthesis.
Interaction of Pro§taglandin§ and Angiotensin II in the Modulation of Renal Function in Congestive Heart Failure M. PACKER, Division of Cardiology, Department of Medicine,
The Mount Sinai School of Medicine of The City University of New York, New York, New York Circulation, suppl. I, 77: I-64-I- 73, 1988 Despite a dramatic fall in renal blood flow, glomerular filtration rate is usually preserved in patients with congestive heart failure until the terminal stages of the disease. This maintanance of renal function appears to be achieved in part the synthesis of two vasoactive factors within the kidney-angiotensin II and prostaglandins-which are rapidly released whenever renal perfusion is compromised or sympathetic nerve traffic to the kidneys is increased. Although these two hormonal systems exert opposite effects on systemic and renal blood flow and sodium and water excretion, both act to preserve glomerular filtration rate: prostaglandins by a vasodilator action exerted primarily on the afferent arteriole and angiotensin II by a vasoconstrictor effect on the efferent arteriole. Consequently, when the synthesis of these hormones is experimentally blocked, renal function deteriorates, especially in subjects with marked renal hypoperfusion and sodium depletion; these two factors interact to determine the importance of intrarenal hormonal release in the modulation of renal function. Clinically, four specific factors have been identified that predispose patients with heart failure to the development of functional renal insufficiency after treatment with converting-enzyme or cyclooxygenase inhibitors: (1) marked renal hypoperfusion, vigintensity orous diuretic therapy, (3) diabetes mellitus, and of hormonal inhibition within the kidney. This last risk factor may provide the basis for differentiating among enzyme-inhibitory drugs and suggests that renal insufficiency in low-output states may be minimized the development of therapeutic agents that block hormonal synthesis selectively at sites that are critical to the disease process but spare the homeostatic tissue-based enzyme systems that exist within the kidney.
Peptide Hormone§ and the Regulation of Sodium Excretion M. H. HUMPHREYS AND S.-Y. LIN, Division of Nephrology and Medical Service, San Francisco General Hospital and Department of Medicine, University of California School of Medicine, San Francisco, California Hypertension, 11: 397-410, 1988
683
control mechanisms for the -.,,,~,- •• ~,- of sodium reabsorption are glomerular filtration rate (including physical factors involving proximal tubular sodium reabsorption) and aldosterone acting on distal tubular reabsorption. Thus, control mechanisms initially were believed to be strictly intrarenal regardless of external factors. However, continuing research with saline expansion and natriuresis without changes in glomerular filtration rate or aldosterone suggested the presence of a circulating natriuretic hormone or "third factor". Currently, it is clear that not 1 but numerous hormonal agents acting directly upon tubular resorption of sodium or indirectly through changes in renal hemodynamics and peritubular physical factors affect sodium reabsorption. This review article summarizes the work in the area with emphasis on atrial natriuretic factor, angiotensin II, vasopressin, anterior pituitary peptides, calcium-regulating peptides and other peptides as they affect sodium reabsorption.
Editorial Comment: These studi.e§ were selected to call omr attention. to the fact that there is mounting evidence for a role of cytokines (cachectin, interleukins, interferons and §O forth) and intrarenal hormones possibly interacting in a va:riety of renal parenchymal disease§. E. Darracott Vaughan, M.D.
Renal a:mi Emfocrine Respon§e in the Elderly During Head-Out Water Immersion 8. 8AGAWA, J. IWAMOTO, K. MIKI, J. R. CLAYBAUGH AND K. SHIRAKI, Department of Physiology,
F, TAJIMA,
School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan and Department of Clinical Investigation, Tripler Army Medical Center, Honolulu, Hawaii Amer. J. PhysioL, 254: R977-R983, 1988 After overnight food and fluid restriction, seven healthy old men were examined (62-74 yr) and eight young (21-28 before, during, and after 3-h head-out immersion (HOI) in thermoneutral water (34.5 ± 0.5°C). On separate days, all subjects remained seated in air for 5 h to obtain the time control data, Although HOI induced a reversible increase in urine flow in all subjects, the response was faster and greater in magnitude in the than in the young. Na excretion and osmolal clearance also followed a response pattern identical to that of urine flow; thus the HO I-induced diuresis was entirely osmotic, Endogenous creatinine clearance increased in the elderly at 2 h of HOI, suggesting an age-related modification in kidney hemodynamics, Although there was virtually the same cephalad blood shift (measured by impedance cardiography), mean arterial pressure significantly increased (P < 0.05) during HOI in the elderly, which also indicated a different response of peripheral circulation to HOI in the elderly. Control level of plasma atrial natriuretic factor (ANF) was nearly twofold greater in the elderly compared with the young. The HOI induced a nearly fourfold increase in ANF in the elderly, whereas that for the young was threefold. Both plasma aldosterone and ADH responses to HOI were attenuated in the elderly compared with the young, which had no correlation with urine flow or Na excretion. It is concluded that the elderly release more ANF at a given cephalad volume expansion compared with the young, but the vasodilative reaction to ANF was attenuated in the elderly.
ritis. To define the regulation of IL-1 synthesis human Northern blot analyses were performed using specific probes for monocytic IL-1 a and (3 mRNA. Proliferating MC expressed mRNA for both IL-1 a and (3, whereas nonproliferating MC contained no detectable IL-1 mRNA. Synchronized MC expressed IL-1 a and (3 mRNA within 2 h of stimulation with serum. This serum effect could be reproduced with plateletderived growth factor and epidermal growth factor. Immune precipitations of ' 5 S-methionine-labeled cells indicate that the mesangial IL-1 is synthesized as a 33-kD precursor protein with a pl of 7.2. Extracellular mesangial IL-1 has a pl of 7.0 and molecular weight of 17 kD, consistent with its identification as IL-1 (3. Cellular proliferation in glomerular disease may be driven in part by peptide growth factor-mediated induction of mesangial IL-1 gene expression and protein synthesis.
Interaction of Pro§taglandin§ and Angiotensin II in the Modulation of Renal Function in Congestive Heart Failure M. PACKER, Division of Cardiology, Department of Medicine,
The Mount Sinai School of Medicine of The City University of New York, New York, New York Circulation, suppl. I, 77: I-64-I- 73, 1988 Despite a dramatic fall in renal blood flow, glomerular filtration rate is usually preserved in patients with congestive heart failure until the terminal stages of the disease. This maintanance of renal function appears to be achieved in part the synthesis of two vasoactive factors within the kidney-angiotensin II and prostaglandins-which are rapidly released whenever renal perfusion is compromised or sympathetic nerve traffic to the kidneys is increased. Although these two hormonal systems exert opposite effects on systemic and renal blood flow and sodium and water excretion, both act to preserve glomerular filtration rate: prostaglandins by a vasodilator action exerted primarily on the afferent arteriole and angiotensin II by a vasoconstrictor effect on the efferent arteriole. Consequently, when the synthesis of these hormones is experimentally blocked, renal function deteriorates, especially in subjects with marked renal hypoperfusion and sodium depletion; these two factors interact to determine the importance of intrarenal hormonal release in the modulation of renal function. Clinically, four specific factors have been identified that predispose patients with heart failure to the development of functional renal insufficiency after treatment with converting-enzyme or cyclooxygenase inhibitors: (1) marked renal hypoperfusion, vigintensity orous diuretic therapy, (3) diabetes mellitus, and of hormonal inhibition within the kidney. This last risk factor may provide the basis for differentiating among enzyme-inhibitory drugs and suggests that renal insufficiency in low-output states may be minimized the development of therapeutic agents that block hormonal synthesis selectively at sites that are critical to the disease process but spare the homeostatic tissue-based enzyme systems that exist within the kidney.
Peptide Hormone§ and the Regulation of Sodium Excretion M. H. HUMPHREYS AND S.-Y. LIN, Division of Nephrology and Medical Service, San Francisco General Hospital and Department of Medicine, University of California School of Medicine, San Francisco, California Hypertension, 11: 397-410, 1988
683
control mechanisms for the -.,,,~,- •• ~,- of sodium reabsorption are glomerular filtration rate (including physical factors involving proximal tubular sodium reabsorption) and aldosterone acting on distal tubular reabsorption. Thus, control mechanisms initially were believed to be strictly intrarenal regardless of external factors. However, continuing research with saline expansion and natriuresis without changes in glomerular filtration rate or aldosterone suggested the presence of a circulating natriuretic hormone or "third factor". Currently, it is clear that not 1 but numerous hormonal agents acting directly upon tubular resorption of sodium or indirectly through changes in renal hemodynamics and peritubular physical factors affect sodium reabsorption. This review article summarizes the work in the area with emphasis on atrial natriuretic factor, angiotensin II, vasopressin, anterior pituitary peptides, calcium-regulating peptides and other peptides as they affect sodium reabsorption.
Editorial Comment: These studi.e§ were selected to call omr attention. to the fact that there is mounting evidence for a role of cytokines (cachectin, interleukins, interferons and §O forth) and intrarenal hormones possibly interacting in a va:riety of renal parenchymal disease§. E. Darracott Vaughan, M.D.
Renal a:mi Emfocrine Respon§e in the Elderly During Head-Out Water Immersion 8. 8AGAWA, J. IWAMOTO, K. MIKI, J. R. CLAYBAUGH AND K. SHIRAKI, Department of Physiology,
F, TAJIMA,
School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan and Department of Clinical Investigation, Tripler Army Medical Center, Honolulu, Hawaii Amer. J. PhysioL, 254: R977-R983, 1988 After overnight food and fluid restriction, seven healthy old men were examined (62-74 yr) and eight young (21-28 before, during, and after 3-h head-out immersion (HOI) in thermoneutral water (34.5 ± 0.5°C). On separate days, all subjects remained seated in air for 5 h to obtain the time control data, Although HOI induced a reversible increase in urine flow in all subjects, the response was faster and greater in magnitude in the than in the young. Na excretion and osmolal clearance also followed a response pattern identical to that of urine flow; thus the HO I-induced diuresis was entirely osmotic, Endogenous creatinine clearance increased in the elderly at 2 h of HOI, suggesting an age-related modification in kidney hemodynamics, Although there was virtually the same cephalad blood shift (measured by impedance cardiography), mean arterial pressure significantly increased (P < 0.05) during HOI in the elderly, which also indicated a different response of peripheral circulation to HOI in the elderly. Control level of plasma atrial natriuretic factor (ANF) was nearly twofold greater in the elderly compared with the young. The HOI induced a nearly fourfold increase in ANF in the elderly, whereas that for the young was threefold. Both plasma aldosterone and ADH responses to HOI were attenuated in the elderly compared with the young, which had no correlation with urine flow or Na excretion. It is concluded that the elderly release more ANF at a given cephalad volume expansion compared with the young, but the vasodilative reaction to ANF was attenuated in the elderly.