Biomedical subjects

M J Peach

Publications and source records attributed to M J Peach.

At least 73 records · Page 4Linked to original sources

PubMed1988

Angiotensin II modulates the intrarenal effects of atrial natriuretic peptide.

The mechanism by which atrial natriuretic peptide (ANP) increases renal water and solute excretion is not fully understood. We studied the renal effects of ANP and angiotensin II (ANG II) separately and together in uninephrectomized conscious dogs (n = 7) in sodium metabolic balance (80 meq/day). Exogenous ANG II and ANP were without measurable systemic effects as demonstrated by absence of changes in blood pressure, plasma aldosterone concentration, and plasma renin activity. The quantity of ANG II that had significant renal effects that were without measurable systemic effects was 0.2 pmol.kg-1.min-1. Three infusion rates of ANP had significant renal effects (1, 10, and 20 pmol.kg-1.min-1). These quantities of ANP caused significant diuresis, natriuresis, kaliuresis, and increased glomerular filtration rate without significant changes in renal plasma flow. ANG II alone caused significant antidiuresis, antinatriuresis, and decreased glomerular filtration rate and renal plasma flow. When ANG II and ANP were given together, no change in urinary flow rate, urinary sodium or potassium excretion, or renal plasma flow was observed, whereas glomerular filtration rate increased. Filtration fraction increased significantly with ANG II and ANP separately and together. Intrarenal ANP prevents the ANG II-induced decrement in urinary sodium excretion and urine flow rate. ANP may play an important role in escape from the sodium-retaining action of intrarenal ANG II.

Aldosterone↗

PubMed1988

Intrarenal renin inhibition increases renal function by an angiotensin II-dependent mechanism.

ACRIP is a competitive inhibitor of renin in which an analogue of statine, (3R,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of porcine renin substrate. ACRIP inhibits the enzymatic activity of renin, thus blocking the initiation of the angiotensin cascade. We studied the intrarenal action of ACRIP in small quantities without measurable systemic effects on renal function. In the first experiment, ACRIP was administered intrarenally at 0.02, 0.2, and 2 micrograms.kg-1.min-1 to uninephrectomized conscious dogs (n = 6) in metabolic balance at sodium intake of 10 meq/day. ACRIP, in doses of 0.02 and 0.2 micrograms.kg-1.min-1, markedly increased urine sodium excretion (UNaV) from 5.8 +/- 1.4 to 15.1 +/- 5.1 and 19.9 +/- 3.2 mu eq/min, respectively. Urinary flow rate (UV) underwent a similar increase and glomerular filtration rate (GFR) increased from 25.7 +/- 2.5 to 35.6 +/- 2.5 at 0.02 micrograms.kg-1.min-1 of ACRIP. Renal plasma flow (RPF), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were not affected. At 2 micrograms.kg-1.min-1, ACRIP traversed the kidney in quantities large enough to produce a reduction in systemic PRA and mean arterial pressure and caused natriuresis, diuresis, and increased GFR. In a second experiment, ACRIP was administered intrarenally at 0.2 micrograms.kg-1.min-1 in a separate group (n = 4) under identical conditions. ACRIP-induced increases in UV and UNaV were completely blocked by concurrent intrarenal administration of angiotensin II. The results indicate that intrarenal angiotensin II acts as a physiological regulator of renal sodium and fluid homeostasis.

Animals↗

PubMed1988

Factors that contribute to resistant forms of hypertension. Pharmacological considerations.

Treatment failure may be caused by induction of compensatory mechanisms that compromise effectiveness of the antihypertensive regimen. Antihypertensive agents have been classified according to mechanism of action, and compensatory mechanisms usually evoked by each class of drugs have been reviewed. Host factors may be responsible for the inability to control blood pressure or may predict special sensitivity or contraindication to a particular class of antihypertensive agents. Recommendations have been made for modification of stepped-care regimens and selection of initial antihypertensive agents based on host factors. Experimental evidence suggests the ability to target antihypertensive therapy in a manner that will prevent or reverse specific end-organ damage. Clinical studies are needed to define the long-term benefit derived from aggressive target organ protection.

Antihypertensive Agents↗

PubMed1988

Location and regulation of rat angiotensinogen messenger RNA.

The presence of angiotensinogen messenger RNA (mRNA) was detected in rat vascular and adipose tissue. Angiotensinogen mRNA in rat aorta was localized in the adventitia and surrounding adipose tissue, and not in the vascular smooth muscle. Freshly dispersed and cultured endothelial and aortic smooth muscle cells did not contain detectable amounts of angiotensinogen mRNA. In addition to periaortic adipose tissue, angiotensinogen mRNA was present in other fat depots of both brown and white types. To examine regulation of angiotensinogen gene expression, Sprague-Dawley rats were treated with angiotensin converting enzyme inhibitor or underwent bilateral nephrectomy. Relative levels of angiotensinogen mRNA in brown adipose tissues increased dramatically by 48 hours after bilateral nephrectomy. However, only one source of brown adipose tissue showed increased angiotensinogen mRNA levels after animals were treated for 5 days with converting enzyme inhibitor. In addition, angiotensinogen was released into the medium from incubated adipose tissues with levels increasing over a 2-hour period. These results demonstrate that angiotensinogen is synthesized by adipose tissue in the rat and may play a role in the function of this tissue.

Adipose Tissue↗

PubMed1988

Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells.

We have explored the hypothesis that contractile agonists are important regulators of smooth muscle cell growth by examining the effects of one potent contractile agonist, angiotensin II (AII), on both cell proliferation and cellular hypertrophy. AII neither stimulated proliferation of cells made quiescent in a defined serum-free media nor augmented cell proliferation induced by serum or platelet-derived growth factor. However, AII did induce cellular hypertrophy of postconfluent quiescent cultures following 4 days of treatment, increasing smooth muscle cell protein content by 20% as compared with vehicle-treated controls. AII-induced hypertrophy was maximal at 1 microM, had an ED50 of 5 nM, and was blocked by the specific AII receptor antagonist Sar1,Ile8 AII. The cellular hypertrophy was due to an increase in protein synthesis, which was elevated within 6-9 hours following AII treatment, while no changes in protein degradation were apparent. AII was even more effective in inducing hypertrophy of subconfluent cultures, causing a 38% increase in protein content after 4 days of treatment (1 microM) and showing a maximal response at concentrations as low as 0.1 nM. Interestingly, in subconfluent cultures, AII treatment (1 microM, 4 days) was associated with a 50% increase in the fraction of cells with 4C DNA content with the virtual absence of cells in S-phase of the cell cycle, consistent with either arrest of cells in the G2 phase of the cell cycle or development of tetraploidy.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1988

Localization of angiotensinogen messenger RNA in rat aorta.

The distribution of angiotensinogen messenger (mRNA) was determined in the rat aorta. Other investigators have demonstrated the presence of angiotensinogen mRNA in whole rat aorta; however, its precise location in the blood vessel wall has not been defined. When various layers of the vessel wall were separated by dissection or cell dispersion, angiotensinogen mRNA levels were greatest in the periaortic adipose tissue. Angiotensinogen mRNA was present in very small levels in the adventitia, with no detectable levels in the muscle layer. In addition to periaortic adipose tissue, angiotensinogen mRNA was also present in the interscapular brown fat pad of the rat. The high levels of angiotensinogen mRNA in periaortic brown adipose tissue suggests that angiotensin may be synthesized there and responses may exist in this tissue or adjacent sympathetic nerve terminals.

Adipose Tissue, Brown↗

PubMed1988

Endothelium-dependent relaxation is independent of arachidonic acid release.

Endothelium-dependent relaxation is mediated by the release from vascular endothelium of an endothelium-derived relaxing factor (EDRF). It is not clear what role arachidonic acid has in this process. Inhibition of phospholipase A2, and diacylglycerol lipase in cultured bovine aortic endothelial cells caused a marked reduction in agonist-induced arachidonic acid release from membrane phospholipid pools, and complete inhibition of prostacyclin production. EDRF release, assayed by measuring endothelium-dependent cGMP changes in mixed endothelial-smooth muscle cell cultures, was not inhibited under these conditions. In fact, EDRF release in response to two agonists, melittin and ATP, was actually increased in cells treated with phospholipase A2 inhibitors. In addition, pretreatment of rats with high-dose dexamethasone, an inhibitor of PLA2, did not attenuate endothelium-dependent relaxation in intact aortic rings removed from the animals, or depressor responses in anesthetized animals induced by endothelium-dependent vasodilators. In summary, inhibition of arachidonic acid release from membrane phospholipid pools does not attenuate endothelium-dependent relaxation in rats, or the release and/or response to EDRF in cultured cells.

Adenosine Triphosphate↗

PubMed1988

Augmentation of hypoxic pulmonary vasoconstriction in the isolated perfused rat lung by in vitro antagonists of endothelium-dependent relaxation.

The role of the endothelium in hypoxic constriction of the intact pulmonary vascular bed has not been clearly elucidated. To test for a possible role for endothelium-derived relaxing factor(s) (EDRF) in the hypoxic pressor response, isolated, whole blood-perfused rat lungs from male Sprague-Dawley rats treated with meclofenamate were prepared. Three protocols were performed, including: (a) normal saline (control); (b) the putative EDRF inhibitors, eicosatetraynoic acid (ETYA, 1 X 10(-4) M) or nordihydroguaiaretic acid (NDGA, 1 X 10(-4) M) versus vehicle DMSO; and (c) the putative EDRF inhibitor hydroquinone (HQ, 1 X 10(-4) M) versus vehicle ethyl alcohol (ETOH). The pulmonary pressor response to angiotensin II (Ang II, 0.25 micrograms) injections alternated with 6-min periods of hypoxic ventilation (3% O2, 5% CO2) was measured before and after the administration of saline, inhibitors, or vehicles. The administration of the EDRF inhibitors ETYA, NDGA, and HQ resulted in a marked accentuation of the hypoxic pressor response that was not seen in the controls (P less than 0.05). In separate experiments, lungs precontracted with norepinephrine (1 X 10(-6) M) were pretreated with edrophonium (1 X 10(-4) M) and then observed for endothelium-dependent vasodilator responses to acetylcholine at increasing doses (1 X 10(-7)-1 X 10(-4) M). Administration of ETYA, NDGA, or HQ abrogated the observed vasodilatation to acetylcholine, which was not seen with vehicles alone (P less than 0.01). These studies suggest an important role for the endothelium in pulmonary vascular responsiveness to alveolar hypoxia through possible release of a relaxing factor(s) that attenuates the degree of pulmonary arterial constriction.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1988

Renal effects of atrial natriuretic peptide infusion in young and adult rats.

The immature kidney appears to be less responsive to atrial natriuretic peptide (ANP) than the mature kidney. It has been proposed that this difference accounts for the limited ability of the young animal to excrete a sodium load. To delineate the effects of age on the renal response to exogenous ANP, Sprague-Dawley rats were anesthetized for study at 31-32 days of age, 35-41 days of age, and adulthood. Synthetic rat ANP was infused intravenously for 20 min at increasing doses ranging from 0.1 to 0.8 microgram/kg/min, and mean arterial pressure, glomerular filtration rate, plasma ANP concentration, urine flow rate, and urine sodium excretion were measured at each dose. Since cyclic GMP acts as a second messenger for ANP action, urinary cyclic GMP excretion also was measured. Increasing doses of ANP caused a similar decrease in MAP at all ages studied, and increased glomerular filtration rate in adult but not young rats. Increasing the dose of ANP from 0.1 to 0.4 microgram/kg/min caused a greater rise in urine flow and urinary cyclic GMP excretion in adult than young rats, and urine sodium excretion increased more in adults at all doses (p less than 0.05). However, the rise in plasma ANP concentration also was greater in adults than in young rats (p less than 0.05), indicative of greater systemic clearance of ANP in young animals. Increasing levels of plasma ANP concentration were correlated with a greater rise in urine flow in adult than young (31-32 day old) rats (p less than 0.05), but there was no differential effect on urinary cyclic GMP excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

Intrarenal effects of [Ala-Pro-Gly-(Ile3-Val5)] angiotensin II in the conscious dog.

Amphibian skin has functional characteristics of epithelium in the mammalian distal nephron and plays an important role in sodium and water metabolism in these animals. A peptide extracted from the skin of the Australian frog Crinia georgiana has been purified, has been determined to have the amino acid sequence of [Ala-Pro-Gly-(Ile3-Val5)]angiotensin II, and recently has been synthesized. We studied the renal effect of synthetic frog skin angiotensin II (FSAII) infused via the renal artery in doses that were confined to the kidney. FSAII was infused intrarenally at 0.2, 2, and 4 pmol/kg.min in uninephrectomized conscious dogs (n = 5) in metabolic balance at a sodium intake of 80 meq/day. FSAII was confined to the kidney, as demonstrated by the absence of any systemic pressor response and/or any increase in plasma aldosterone concentrations during intrarenal FSAII infusion at rats of 0.2 and 2 pmol/kg.min. At 4 pmol/kg.min, FSAII traversed the kidney in amounts sufficient to stimulate aldosterone secretion (P less than 0.05). All three doses of FSAII caused significant antidiuresis and antinatriuresis, and decreased fractional excretion of sodium. There were no changes in the glomerular filtration rate (GFR) or renal plasma flow (RPF) during FSAII infusion at 0.2 and 2 pmol/kg.min. At 4 pmol/kg.min, FSAII engendered a significant decrease in GFR and RPF, while the filtration fraction increased. There were no significant changes in arterial blood pressure at any dose of FSAII. When confined to the kidney, FSAII caused antidiuresis and anti-natriuresis in the absence of a change in GFR and RPF. These results provide evidence that angiotensin acts directly at the renal tubular level to alter renal function.

Angiotensins↗

PubMed1988

Fetal expression of the angiotensinogen gene.

To determine whether the angiotensinogen (Ao) gene is expressed in multiple organs of the fetal rat and the changes associated with maturation, fetal (15-20 days of gestation), newborn (1-10 days old), and adult (90 days old) rat tissues were subjected to Northern analysis and hybridization with a full length Ao complementary DNA (cDNA). Whereas Ao messenger RNA (mRNA) was undetectable in fetal livers, Ao sequences were readily detectable 1 h after birth and reached a peak at 24 h of birth. Levels remained elevated at 5 and 10 days after birth to decrease slightly at 90 days of postnatal life. Poly A+ enriched liver RNA was subjected to a similar analysis demonstrating that fetal liver Ao mRNA levels were 50-fold less than the corresponding adult levels. In contrast to the finding in the fetal liver, Ao mRNA was found in fetal brown fat, brains, and kidneys. We conclude that 1) Expression of the Ao gene is developmentally regulated in a tissue-specific manner; 2) Unlike the adult animal, the liver may not be the primary source of Ao in the fetus; 3) Alternate sources of Ao synthesis include fetal brown fat, brain, and kidneys.

Adipose Tissue, Brown↗

PubMed1988

Para-bromophenacyl bromide inhibits endothelium-dependent arterial relaxation and cyclic GMP accumulation by effects produced exclusively in the smooth muscle.

The alkylating agent para-bromophenacyl bromide (PBPB) has been reported to block endothelium-dependent relaxation of arteries, presumably by inhibiting phospholipase in the endothelium. We have investigated the site of action of PBPB-induced inhibition of melittin (MEL)- and bradykinin (BK)-stimulated endothelium-dependent relaxation and vascular smooth muscle (VSM) cyclic GMP (cGMP) accumulation. Studies were performed using short-term co-cultures of bovine pulmonary artery endothelial cells (EC) grown on microcarrier beads and rat aortic VSM. The culture system allowed separate pretreatment of ECs and VSM cells with PBPB (3 X 10(-5) M) before placement of the two cell types in co-culture. Because PBPB is an alkylating agent, it was felt that any blockade would endure after washout. Intracellular (VSM) concentrations of cGMP rose in response to MEL or BK stimulation only when EC were present, and were not decreased when only the EC had been pretreated with PBPB. cGMP accumulation induced by MEL or BK was significantly (P less than .01) inhibited in co-cultures where either the VSM alone or VSM and EC combined were pretreated with PBPB. The PBPB pretreatment adequately blocked EC phospholipase activity as measured by attenuation of the release of [3H]arachidonate from prelabeled EC by MEL. In parallel studies, when endothelium-derived relaxing factor was transferred by superfusion of EC to denuded rabbit aortic rings contracted with phenylephrine and pretreated with PBPB, the relaxation response induced by MEL or BK was inhibited. Similarly, when endothelium-derived relaxing factor was transferred to wells of cultured VSM pretreated with PBPB, cGMP accumulation was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetophenones↗

PubMed1988

Intrarenal dopamine-1 receptors control renal function.

Dopamine receptors are classified to DA-1 and DA-2 and are characterized in renal tissue by radioligand binding and by the response of renal adenylate cyclase to dopaminergic agonists and antagonists. DA-1 receptors are localized in the renal tubules, the medial layer of renal microvessels, and the juxtaglomerular apparatus. DA-1 receptor stimulation causes dilation of renal, mesenteric, coronary, and cerebral vessels. In the present study, we tested the hypothesis that dopamine is a paracrine substance in the control of renal function. We employed a potent specific DA-1 receptor antagonist, SCH, to evaluate the role of intrarenal DA-1 receptor in the maintenance of renal function. Intrarenal DA-1 receptor blockade with SCH caused a highly significant dose-dependent antidiuresis and antinatriuresis, and decreased FENa. A rebound diuresis and natriuresis above control values were observed after cessation of DA-1 receptor blockade. There were no changes in renal hemodynamic function during DA-1 receptor blockade. These results strongly suggest that the antinatriuresis and antidiuresis induced by DA-1 receptor blockade are mediated by an action at the renal tubule. The infusion rate of SCH administered intrarenally was sufficiently low to produce no measurable systemic effects including PRA, PAC, and MAP. Thus, these results can be interpreted as due to intrarenal DA-1 blockade. In summary, we have demonstrated that renal excretory function is highly sensitive to DA-1 receptor blockade within the kidney and appears to be mediated by renal tubular events. This study provides strong evidence that DA-1 receptors play a physiological role in the control of renal function.

Animals↗

PubMed1988

Correlation of parameters of urinary excretion with serum osmolality among patients with psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome).

Nine patients (seven men and two women, mean age 36.3 +/- SD 6.7 years), six of whom had schizophrenic disorders, two of whom had bipolar disorder (manic-depressive illness), and one of whom had schizoaffective disorder, manifested psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome). Their stable pattern of hyposthenuria allowed us to predict 24-hr urinary volume on the basis of estimated daily urinary creatinine and early morning urinary creatinine concentration. Lithium and carbamazepine (Tegretol) had little, if any, effect on polyuria. Correlations of parameters of urinary excretion with serum osmolality among our nine PIP patients failed to implicate water consumption as the exclusive cause of serum hypoosmolality and attendant complications usually ascribed to "water toxicity" in the PIP syndrome. Discussed, also, is the overlap of the clinical and laboratory features of the PIP syndrome with the clinical and laboratory features of both diabetes insipidus and the syndrome of inappropriate antidiuresis.

Adult↗

PubMed1987

Changes in vascular endothelium and its function in systemic arterial hypertension.

The various functions of arterial endothelium may be altered during pulmonary and arterial hypertension. Changes in the endothelium (or function) associated with hypertension are described. In both acute and chronic hypertension, permeability of the endothelium is enhanced. During the acute phase of hypertension, hyperplasia (cell replication) of the endothelium occurs while cell hypertrophy (enlarged cell size) and an increase in homocellular tight junctions are associated with sustained elevations of blood pressure. Endothelium may contribute to the increase in smooth muscle mass or cell number reported with various models of hypertension. Increased endothelial uptake or metabolism of norepinephrine and serotonin occurs during hypertension. The biotransformation of adenine nucleotides and various peptides by the endothelium is not altered by hypertension. Synthesis of prostacyclin is enhanced in the spontaneously hypertensive and Goldblatt hypertensive rat. Metabolism of prostaglandin E2, prostaglandin F2 alpha and prostacyclin by prostaglandin 15-hydroxydehydrogenase is impaired in the genetic models. Responses to endothelium-dependent vasodilators are impaired in acute and chronic models of hypertension. Production of relaxing factor by the endothelium is not inhibited, but rather the vascular smooth muscle fails to respond. Acute, severe hypertension potentiates the response to serotonin, presumably by attenuating the release or response to relaxing factor(s). In the aorta of the spontaneously hypertensive rat, the endothelium releases a constricting factor in response to acetylcholine. Pulmonary arterial endothelium (and other vessels) releases a vasoconstrictor that is blocked by inhibitors of cyclooxygenase. It is not clear whether this pressor factor is thromboxane A2. Cultured endothelial cells release a polypeptide that contracts arteries; however, any relation to hypertension is not known.

Acute Disease↗

PubMed1987

Role of calcium in endothelium-dependent relaxation of arterial smooth muscle.

Endothelium-dependent relaxation was studied in rings of rabbit thoracic aorta. Relaxation responses were induced with methacholine, the calcium ionophore A23187 and maitotoxin before and after removal of Ca++ from the external medium; in the presence of calcium-channel entry blockers (verapamil and nifedipine); or with trifluoperazine. Deletion of Ca++ greatly impaired responses to all 3 agonists while trifluoperazine only blocked cholinergic-induced relaxation. The calcium-channel blockers had effects that were concentration- and time-dependent, but their action included blockade of A23187. Cytosolic-free Ca++ concentrations were measured in cultured endothelial cells after incubation of the cells with 10 microM Fura-2/AM or 50 microM Quin 2/AM. Bradykinin (1 X 10(-10) to 1 X 10(-7) M) and melittin (0.5 to 5 micrograms/ml) caused dose-dependent increases in intracellular Ca++ with maximal responses at 3 X 10(-8) M and 3 micrograms/ml, respectively. Both agents were able to induce an increase in cytosolic-free Ca++ in the presence of EGTA (1.5 X 10(-3) M) or verapamil (1 X 10(-5) M). The plateau phase of the Ca++ transient appeared to be modified slightly by verapamil, while the peak responses and plateau were attenuated by '0' Ca++/EGTA. To assess a function of the endothelium, production of endothelium-derived relaxing factor (EDRF) was studied in cells grown on microcarrier beads superfused in a column, and the column effluent was bioassayed on aortic rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Fetal expression of muscle-specific isoactins in multiple organs of the Wistar-Kyoto rat.

Actin, a cytoskeletal and contractile protein, is expressed in six different isoforms that exhibit striking specificity. No studies have considered the muscle-specific actin expression in multiple organ systems in the intact fetus. Using a monoclonal antibody (B4) which reacts specifically with the isoactins of the smooth and skeletal muscle our immunohistochemical study examined whole fetal body sections to follow the development of actin expression throughout the last third of gestation in the Wistar-Kyoto rat. B4 staining was exclusively localized to muscle, confirming its high specificity and its usefulness for studying the ontogeny of muscle-specific isoactins. At 15 days of gestation, B4 staining was detected in the heart, the thoracic aorta and the skeletal muscle of the chest wall. The distribution and intensity of staining in the heart were initially higher than in the aorta or skeletal muscle and remained unchanged throughout the remainder of gestation, suggesting that the maturation of cardiac actin expression is well developed, although not fully completed before birth. Expression of muscle-specific actins in skeletal muscle was age-dependent and correlated with the maturational changes of muscle cell precursors. B4 staining in the fetal kidney was not apparent until day 20 of gestation and was localized to the inner cortical vessels. in association with the most mature nephrons, suggesting a centrifugal maturation of the intrarenal vasculature. The intensity of B4 staining in most tissues including bronchi, bowel, diaphragm, chest wall muscle and peripheral and pulmonary arteries increased by the end of gestation.

Actins↗

PubMed1987

Isolation of renin-rich rat kidney cells.

Enzymatic dispersion and density gradient (Percoll) sedimentation were used to isolate a population of renin-containing, granule-laden cells (density 1.067 g/ml) from rat kidney cortex. Using immunohistochemistry (light microscopy) and electron microscopy, we defined the presence and ability of these cells to store renin protein(s). A 1000 base pair rat renin complementary DNA was used to show that these cells express the renin gene. The reverse hemolytic plaque assay defined the functional properties of the renin-containing cell. The data are consistent with the postulated inverse relationship between calcium concentration and release of renin. Thus, we have isolated a population of functional rat kidney cells that synthesize, store, and release renin.

Animals↗