Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the relationship between the elevation of blood pressure and altered bone metabolism, the changes of systolic blood pressure in six experimental models for bone disorders were investigated. Rats used were either parathyroidectomized, ovariectomized, fed with a calcium-deficient diet, fed with a vitamin D-deficient diet, treated with HEBP (1-Hydroxyethylidene-1, 1-bisphosphonate) or treated with streptozotocin. Hypertension developed in 5-week-old male rats fed with a calcium-deficient diet for 2 weeks, which evoked hypocalcemia and nutritional hyperparathyroidism. The blood pressure returned to normal when fed with a normal calcium diet. In parathyroidectomized rats receiving a normal calcium diet, the blood pressure did not rise, though the plasma calcium level decreased to an extent similar to the rats fed with the calcium-deficient diet. These findings seem to indicate that hyperparathyroidism, but not hypocalcemia, was involved in the elevation of blood pressure in rats fed with a calcium-deficient diet. Hypertension was not observed in rats fed with a vitamin D-deficient diet or treated with streptozotocin. These rats showed not only an increase in parathyroid hormone (PTH) but also a decrease in 1,25 (OH)2 D3. These results may suggest that the presence of 1,25 (OH)2D3 as well as the enhanced parathyroid function is necessary for the development of hypertension. The elevated blood pressure was reduced by a calcium antagonist, nifedipine, or by calcium supplementation, but not by an inhibitor of angiotensin-converting enzyme, captopril, or by calcitonin. This may indicate that hypertension due to nutritional hyperparathyroidism responds to the calcium antagonist nifedipine and to calcium supplementation, but does not depend on renin or salt. Furthermore, an acute hypotensive effect by human PTH (1-34) was not observed in the hypertension of calcium-deficient rats, suggesting the difference between acute and chronic effects of PTH. The hypertension developed in the present experiment may be a useful model for pharmacological evaluation of antihypertensive drugs, such as calcium and calcium antagonists.
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PMID:[Pharmacological study on blood pressure in rats with bone disorders]. 253 55

Basolateral membranes were prepared from rat renal cortex by density gradient centrifugation. Their purity was confirmed by electron microscopy and by marker enzyme enrichment. The basolateral membrane preparation was shown to be derived predominantly from the proximal renal tubule by measurement of hormone-stimulated adenylate cyclase; marked stimulation of adenylate cyclase was found with parathyroid hormone, but not with isoprenaline, antidiuretic hormone or calcitonin. A single class of specific high-affinity [3H]angiotensin II-binding site was identified in the basolateral membrane preparation which, after correction of results for tracer degradation, showed equilibrium dissociation constant of 0.23 nmol/l and binding site concentration of 485.8 fmol/mg protein. Binding sites for [3H]angiotensin II were measured in basolateral membranes prepared from rats fed diets with a low, normal or high sodium content. A trend of increased binding site density with reduced sodium intake was found which did not reach statistical significance. No effect on affinity was demonstrated. Treatment of rats on a low-sodium diet with captopril (500 mg/l drinking water) caused a significant reduction in binding site density; no effect on affinity was demonstrated. These findings suggest that the density of angiotensin II receptors at this site is altered by the activity of the renin-angiotensin system.
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PMID:[3H]angiotensin II binding to basolateral membranes from rat proximal renal tubule: effect of sodium intake and captopril. 254 61

Cardiovascular and renal actions of human calcitonin gene-related peptide II (or beta) (CGRP) and of human calcitonin (CT) infused intravenously for 1 h each (79 and 263 pmol.kg-1.h-1) have been compared in normal men (n = 10 for CGRP, n = 6 for CT and vehicle alone). CGRP lowered diastolic blood pressure by 26% and increased the heart rate by 35% and raised plasma levels of norepinephrine, epinephrine, and dopamine and renin activity (P less than 0.01). The fractional excretion rates (FE) of sodium and chloride were doubled (P less than 0.05-0.01) in the presence of an unaltered glomerular filtration rate. CT, on the other hand, did not affect the diastolic blood pressure, but the stimulation of diuresis and of the FE of sodium and chloride was more pronounced with CT than with CGRP (P less than 0.01). Moreover, CT lowered serum calcium levels and stimulated urinary adenosine 3',5'-cyclic monophosphate and phosphate excretion (P less than 0.01). In conclusion, the cardiovascular effects of CGRP are contrasted by weaker renal tubular actions of the neuropeptide in relation to CT.
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PMID:Distinct hemodynamic and renal effects of calcitonin gene-related peptide and calcitonin in men. 255 73

We investigated the relation of calcitonin as a calcium-active hormone to its more recently described effects on peripheral vascular tone. Basal renal renin secretion in vitro in rat kidney slices was studied in the presence of salmon calcitonin (SCT, 4400 U/mg), amino acid substituted analogues of SCT, 16-alanine SCT (6200 U/mg) and 12,16,19 tri-alanine SCT (350 U/mg), and of rat calcitonin gene-related peptide (rCGRP). All calcitonin species at the same hypocalcemic activity (1 U/mL) modestly but significantly suppressed renin secretion from control levels (9.79 +/- 0.44 to 7.51 +/- 0.53, 7.70 +/- 0.72, and 7.78 +/- 0.90 Goldblatt units/g/h for SCT, 16-ala SCT, and tri-ala SCT, P less than .05 for all calcitonins v control), whereas rCGRP had no effect. Thus, on a molar basis, the renin suppressing effects of the various calcitonin species paralleled their bioassay-defined calcium sequestering activity, 16-ala SCT greater than SCT much greater than tri-ala SCT. Lower concentrations of SCT (10(-2) U/mL and 10(-4) U/mL, approximately 6 X 10(-10) and 6 X 10(-12) mol/L, respectively) had virtually identical effects. Moreover, verapamil (5 X 10(-6) mol/L) blocked the SCT-induced suppression of renin secretion (9.79 +/- 0.44 v 9.36 +/- 1.05 GU/g/h, P = NS). We conclude that the juxtaglomerular apparatus is a calcitonin-responsive system, in which calcitonin and its analogues act to suppress basal renin secretion in vitro. This effect seems to depend on and may be mediated by modulating cellular calcium uptake, and suggests a wider, calcium-related role for calcitonin than had previously been suspected.
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PMID:Effects of calcitonin, calcitonin analogues, and calcitonin gene-related peptide on basal in vitro renin secretion. 266 71

The systemic cardiovascular and renal effects of synthetic beta-human calcitonin gene-related peptide (beta-hCGRP) were examined in conscious normotensive and one-kidney one-clip (1K-1C) hypertensive dogs. beta-hCGRP was infused intravenously at 10 and 50 ng/kg/min for 75-min periods each. Mean arterial pressure did not change significantly (p greater than 0.05) in either group during low dose infusion of beta-hCGRP, but infusion of beta-hCGRP at 50 ng/kg/min produced a fall in mean arterial pressure from 140 +/- 4 to 116 +/- 6 mmHg (p less than 0.05) in the hypertensive dogs (n = 4) and from 100 +/- 4 to 78 +/- 3 mmHg (p less than 0.05) in the normotensive dogs (n = 4). Heart rates increased significantly during infusion of beta-hCGRP in both groups. Also, renal sodium and potassium excretion decreased (p less than 0.05) in the two groups at both the low and high doses of beta-hCGRP. Creatinine clearance was unchanged in normal dogs and decreased (p less than 0.05) in 1K-1C hypertensive dogs at the high rate of beta-hCGRP infusion. The clearance of p-aminohippurate increased approximately 20% (p less than 0.05) in both groups with the low dose infusion of beta-hCGRP but further increases were elicited only in the normotensive dogs in response to the elevation in the beta-hCGRP infusion rate. Plasma renin and aldosterone levels increased (p less than 0.05) above control levels during the maximum hypotensive response to beta-hCGRP infusion in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiovascular and renal effects of calcitonin gene-related peptide in hypertensive dogs. 267 14

Calcitonin gene-related peptide (CGRP) is localized in capsaicin-sensitive nerve fibres in the kidney and urogenital tract whereas calcitonin reaches the kidney through the general circulation. Systemic infusion of CGRP and perfusion of isolated rat kidney reduces vascular resistance, and increases renal blood flow and glomerular filtration. CGRP stimulates renin secretion in vivo and in vitro and inhibits contraction of isolated rat mesangial cells by angiotensin II. Calcitonin does not affect vascular resistance, renal blood flow and glomerular filtration, and is less potent in stimulating renin secretion, and does not alter contraction of isolated rat mesangial cells by angiotensin II. CGRP also exerts renal tubular effects brought about probably through interaction with calcitonin receptors. To this end, increased excretion of sodium and chloride, and stimulation of urinary flow are less pronounced with CGRP than with calcitonin. Calcitonin, moreover, stimulates the fractional urinary excretion of calcium and phosphate.
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PMID:Calcitonin gene products and the kidney. 268 65

The dose-response effects of infused calcitonin gene-related peptide (CGRP), a potent vasodilator, on systemic and regional hemodynamics in the conscious rat remain incompletely defined. The radioactive microsphere technique provided these determinations before and after the intravenous administration of vehicle or 22, 65, 220, and 2200 pmol of CGRP. Neither vehicle nor 22 pmol of CGRP significantly changed any systemic or regional hemodynamic parameter. Starting at the 65-pmol dose, CGRP significantly decreased mean blood pressure and total peripheral resistance, while increasing heart rate without changing cardiac output. CGRP produced selective regional vasodilatory effects, with the coronary circulation being unusually sensitive. In contrast, CGRP caused significant increases in blood flow to the mesenteric and cutaneous circulations only at the two highest doses. CGRP increased plasma norepinephrine, epinephrine, and renin activity significantly at only the 2200-pmol dose. In conclusion, CGRP decreases blood pressure by peripheral vasodilation, with a threshold dose occurring between 22 and 65 pmol. In addition, the coronary circulation appears to be particularly sensitive to the vasodilatory properties of CGRP.
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PMID:Dose-dependent systemic and regional hemodynamic effects of calcitonin gene-related peptide. 278 32

This study examined the effects of calcitonin gene-related peptide (CGRP) on aldosterone secretion both in vivo and in vitro. Intravenous administration of CGRP (0.01 micrograms/kg) in 6 conscious dogs produced a significant decrease in plasma aldosterone concentration from 68 +/- 12 pg/ml to 28 +/- 11 pg/ml (p less than 0.05) despite a mild but significant elevation of plasma renin activity. In an in vitro study using isolated rabbit adrenal glomerulosa cells CGRP reduced the basal aldosterone secretion in a dose-related manner and furthermore 10(-9) M CGRP inhibited the aldosterone secretion stimulated by 10(-8) M angiotensin II. From these results it is suggested that CGRP has an inhibitory effect on aldosterone secretion.
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PMID:Calcitonin gene-related peptide is an inhibitor of aldosterone secretion. 279 89

A role for calcium in human hypertensive disease has been suggested. However, the various, apparently contradictory, abnormalities of calcium metabolism observed in experimental and clinical hypertension do not allow for unambiguous description of the specific manner in which calcium contributes to the hypertensive process. We studied calcium metabolism in essential hypertension and used renin-sodium profiling, which reveals the biochemical heterogeneity of clinical hypertension. We observed renin-linked, heterogeneous deviations in circulating levels of the divalent cations, magnesium and ionized calcium, in addition to deviations in the calcium-regulating hormones, parathyroid hormone (PTH), calcitonin (CT), and 1,25 dihydroxyvitamin D (1,25 D). These renin-calcium metabolic deviations may both predict and contribute to the pathophysiology of salt-induced hypertension, the blood pressure effects of oral calcium supplementation, as well as the short and longer term effectiveness of calcium channel blockade. Altogether, these data suggest an intimate linkage between the hormonal control of calcium metabolism, the renin-angiotensin system and blood pressure regulation in human hypertension.
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PMID:The significance of calcium and calcium channel blockade in essential hypertension. 285 82

The renin-angiotensin-aldosterone system regulates blood pressure and volume homeostasis in addition to sodium and potassium metabolism, and may be linked to divalent cation metabolism as well as hypertensive disease. In essential hypertension, circulating serum magnesium and Ca++, and the calcium regulating hormones, parathyroid hormone, calcitonin and 1,25 dihydroxyvitamin (1,25D) are different in the various renin subgroups. Elevated blood pressure induced by such maneuvers as dietary salt loading is associated with exacerbations of these calcium metabolic deviations, and appears related to salt-induced changes in serum Ca++ or 1,25D levels. Short- or longer-term lowering of blood pressure with the calcium-channel blocker, nifedipine, or with calcium or magnesium supplementation is associated with a shift of renin system activity and calcium metabolic indexes back to average normotensive values in those subjects most susceptible to these hypotensive agents. These observations suggest that deviations in calcium metabolism in essential hypertension may be related to the pathophysiology of the hypertensive process. Further, renin system activity and calcium metabolic indexes such as serum Ca++ levels may help target specific subgroups of hypertensive populations most susceptible to various dietary or drug maneuvers, and thus may provide a basis to better understand and treat clinical hypertension.
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PMID:Renin, calcium metabolism and the pathophysiologic basis of antihypertensive therapy. 286 7


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