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S A Atlas

Publications and source records attributed to S A Atlas.

At least 73 records · Page 4Linked to original sources
PubMed1986

Carotid baroreceptor unloading decreases plasma atrial natriuretic factor in hypertensive patients.

Atrial natriuretic factor (ANF) release is known to be regulated by distension of the atrial wall; other factors affecting ANF secretion have not yet been defined. In order to evaluate the effects of the reflex activation of the sympathetic nervous system on ANF plasma levels, in 11 patients with essential hypertension progressive deactivation of carotid baroreceptors was induced by 4-min graded increases in external neck tissue pressure. Carotid sinus hypotension induced progressive increases in blood pressure (BP), heart rate (HR) and forearm vascular resistance (FVR), while plasma renin activity and catecholamine concentrations did not change significantly. Despite the lack of changes in right atrial pressure during this manoeuvre, plasma ANF levels showed a progressive and significant reduction, which was correlated with the increase in FVR. Although a contribution by other factors cannot be ruled out, our data suggest that the reflex activation of sympathetic nervous system is associated with reduced ANF release, independent of changes in atrial pressure.

Adult↗
PubMed1986

Renal hemodynamic and natriuretic effects of atrial natriuretic factor.

In this article we review the renal hemodynamic and excretory actions of atrial natriuretic factor (ANF) and consider some of the mechanisms of its vascular and natriuretic effects. ANF leads to a marked, sustained, and parallel increase in whole-organ and superficial single-nephron glomerular filtration rate (GFR) while mean blood pressure is decreased and renal blood flow (RBF) is unchanged or even decreased. The increase in GFR is caused by an efferent arteriolar vasoconstriction or by a combination of afferent vasodilation and efferent vasoconstriction. ANF also leads to a decrease in the hypertonicity of the innermedullary interstitium. Together with the increase in GFR, this phenomenon accounts wholly or in great part for the ANF-induced natriuresis. The overall renal vascular effects of ANF are complex and may tentatively be conceptualized as a behavior of a functional partial agonist: slight vasoconstriction in vasodilated kidneys, no sustained effects on the vascular resistance in normal kidneys, and vasodilation in vasoconstricted kidneys. The vasoconstrictor effect of ANF may be direct or indirect and depends on extracellular calcium whereas the antagonist effect likely results from alterations in intracellular calcium homeostasis. The data raise the perspective that ANF is not only a powerful natriuretic substance but has the potential of being an important modulator of GFR and RBF in intact animals.

Aldosterone↗
PubMed1986

Acid-activatable inactive renin in cat plasma and kidney.

Inactive renin has been identified in cat plasma and kidney extracts. It is identical to human plasma prorenin in all respects tested except that the pH optimum of activated cat inactive renin is slightly different from that of active renin. To further investigate whether cat inactive renin is indeed prorenin we examined whether it could be reversibly acid-activated, an unusual characteristic of human prorenin. We found that dialysis of partially purified, cat renal inactive renin to pH 3.3 caused reversible acid activation. In plasma, when acidification was followed by a second dialysis to pH 7.4 at 4 degrees C, irreversible activation took place, just like human prorenin. Unlike human angiotensinogen, cat angiotensinogen was apparently not affected by acid dialysis. These results suggest that cat inactive renin is most likely prorenin.

Animals↗
PubMed1985

Immunological evidence that inactive renin is prorenin.

Antibody raised to a synthetic dodecapeptide, corresponding to the C-terminal portion of the human renin pro-segment, was tested for its ability to recognize highly purified human inactive or active (mature) renins; immune complexes were detected by precipitation with protein A-Sepharose. Serial antibody dilutions caused identical binding of renal or plasma inactive renins but failed to bind active renin. In contrast, antibody to active renin recognized both active and inactive forms. Reversible acid activation of inactive renin enhanced its binding to the anti-prorenin antibody, whereas irreversible trypsin activation significantly reduced binding. Binding was abolished following prolonged exposure to trypsin or if inactive renin was acidified prior to trypsin treatment. These results indicate that inactive renin shares immunochemical determinants with prorenin; they suggest that acidification alters the conformation of the pro-segment and that trypsin can convert the molecule both to fully mature renin and to intermediate form(s).

Animals↗
PubMed1985

Plasma prorenin in first-trimester pregnancy: relationship to changes in human chorionic gonadotropin.

Prorenin and human chorionic gonadotropin are both synthesized in chorionic cells. The relationship of changes in maternal plasma prorenin to changes in human chorionic gonadotropin were therefore evaluated during the first trimester. In samples submitted to the routine chemistry laboratory for detection of pregnancy a positive relationship was observed between prorenin and beta human chorionic gonadotropin during the 5 weeks following conception. Subsequently human chorionic gonadotropin continued to rise but prorenin had reached a plateau. Serial studies in one subject demonstrated that prorenin had increased to 65% of maximum by the thirteenth day following conception whereas human chorionic gonadotropin had risen to only 0.2% of maximum. By 3 to 5 days post partum, beta human chorionic gonadotropin had fallen by 98% but prorenin had fallen by only 50%. The early rise in prorenin following conception and the relatively slow fall post partum suggest that pregnancy-related changes in maternal plasma prorenin are of maternal, not fetal, origin.

Chorionic Gonadotropin↗
PubMed1985

Effects of atrial natriuretic factor on human platelet function.

We examined the hypothesis that atrial natriuretic factor (ANF), a substance with known vasorelaxant activities, shares with other vasodilators the property of inhibiting platelet function. Aggregation of citrated platelet-rich plasma (PRP) from 23 healthy volunteers induced by ADP, adrenaline, arachidonic acid, collagen, gamma-thrombin, the endoperoxide analogue U-44069, serotonin, the calcium ionophore A-23187 or platelet aggregating factor was measured after incubation of PRP with ANF for 3 minutes at concentrations of 4 X 10(-9), 4 X 10(-8) and 4 X 10(-7) M or vehicle as control. ANF decreased ADP-induced aggregation significantly (P less than 0.02), but only at the highest concentration used and to a minor extent (control: 73.6 +/- 11.2%; after ANF 4 X 10(-7) M: 60.0 +/- 17.1%, mean +/- S.D., n = 39) by a selective inhibitory effect on the secondary wave; neither aggregation by all other agents tested nor thromboxane B2 generation induced by ADP and adrenaline was altered by incubation with ANF. Although ANF thus has detectable effects on ADP-induced platelet aggregation in vitro, these data suggest that ANF is unlikely to be a physiologically significant modulator of platelet function.

Adenosine Diphosphate↗
PubMed1985

Immediate converting-enzyme inhibition with intravenous enalapril in chronic congestive heart failure.

To test the hypothesis that intravenous enalapril is a useful pharmacologic probe of the renin angiotensin system, intravenous enalapril was administered to 9 patients with severe congestive heart failure (CHF). This produced abrupt and complete blockade of converting enzyme, with peak effect occurring at 30 minutes, as reflected by increases of plasma renin activity (from 16.8 +/- 6 to 86.6 +/- 23 ng/ml/hour) and decreases of plasma aldosterone levels (from 46 +/- 14 to 25 +/- 6 ng%) (both p less than 0.05). With reduction of angiotensin II--mediated vasoconstriction, systemic vascular resistance decreased markedly (from 1,974 +/- 233 to 1,400 +/- 136 dyne s cm-5) and cardiac index was improved (from 1.88 +/- 0.9 to 2.20 +/- 0.21 liters/min/m2) (both p less than 0.05). The time course of angiotensin II levels suggested that the lack of a cumulative effect from additive doses of intravenous enalapril was a reflection of complete inhibition of converting enzyme. One patient did not respond to enalapril; despite comparable hemodynamic severity of CHF, the renin-angiotensin system was not activated in this patient. Thus, intravenous enalapril is capable of rapid and complete inhibition of converting enzyme for the accurate assessment of angiotensin II--mediated vasoconstriction in patients with severe CHF.

Adult↗
PubMed1985

Cyclical secretion of prorenin during the menstrual cycle: synchronization with luteinizing hormone and progesterone.

Plasma prorenin, a high molecular weight precursor form of renin, (renin, EC 3.4.23.15; old number, EC 3.4.99.19), was measured three times weekly in normal young women during the menstrual cycle and was related to changes in luteinizing hormone, estradiol, and progesterone. In all subjects a stable baseline level of prorenin occurred during the follicular phase. Then, simultaneously or soon after the luteinizing hormone peak, plasma prorenin consistently increased about 2-fold. Baseline prorenin ranged from 18 to 40 ng per ml per hr, and peak prorenin ranged from 35 to 65 ng per ml per hr. The maximum increase in prorenin averaged 80%. Prorenin remained elevated during the mid-luteal phase of the menstrual cycle and returned to baseline during the late-luteal phase in coordination with the decrease in progesterone. The changes in prorenin were not synchronized with changes in active renin which was significantly increased only during the mid-luteal phase. These findings suggest that prorenin may be involved in reproductive physiology.

Enzyme Precursors↗
PubMed1985

Effect of atrial natriuretic factor on renin secretion, plasma renin and aldosterone in dogs with acute unilateral renal artery constriction.

Atrial natriuretic factor (ANF) decreases renin secretion rate (RSR), plasma renin activity (PRA) and plasma aldosterone (PA) in normal dogs. To clarify further the mechanisms responsible for these effects, the left renal artery was constricted in seven anaesthetized dogs prior to ANF administration. Constriction of the left renal artery decreased (P < 0.05) ipsilateral mean renal perfusion pressure (MRPP, 29 +/- 7%), renal plasma flow (RPF, 42 +/- 11%) and glomerular filtration rate (GFR) and filtered sodium load (FLNa, 21 +/- 8.8%). Ipsilateral RSR and peripheral PRA tended to increase, although not significantly. Atrial natriuretic factor infusion did not alter GFR in the clamped kidney and failed to decrease RSR or PRA. Despite this, PA levels decreased significantly (7.8 +/- 2.4 to 5.6 +/- 1.8 ng%). These results suggest that ANF-induced inhibition of renin secretion is largely consequent on its renal haemodynamic actions and that suppression of aldosterone by ANF in vivo is due, in part, to direct effects on the adrenal cortex.

Aldosterone↗
PubMed1985

Atrial natriuretic factor (auriculin): structure and biological effects.

Atrial natriuretic factor (ANF) is a recently discovered peptide present in secretory granules specifically found in atrial muscle cells. Multiple structurally related peptides have been isolated from atrial tissues, all of which are derived from a common 152-amino-acid precursor. ANF induces profound natriuresis and diuresis in experimental animals and also causes relaxation of precontracted vascular smooth muscle. ANF has striking renal hemodynamic actions (most consistently an increased glomerular filtration rate), which probably explain its natriuretic effects. ANF also can inhibit renin secretion in vivo and causes direct inhibition of basal and stimulated aldosterone production. It lowers arterial blood pressure, probably reflecting in part its vasorelaxant actions, and this effect is particularly marked in renin-dependent (and possibly other vasoconstricted) models of hypertension. Although the exact structure and regulation of the presumed circulating form(s) of ANF remain to be clarified, available information suggests that it may be a new, previously unrecognized factor in the regulation of fluid volume and renal and cardiovascular function.

Aldosterone↗
PubMed1984

Actions of synthetic atrial natriuretic factor on bovine adrenal glomerulosa.

Synthetic atrial natriuretic factor (ANF) inhibited aldosterone production by suspensions of bovine adrenal glomerulosa cells. Inhibition by ANF was most pronounced when basal aldosterone production was measured. The effects of angiotensin II (AII), N6,O2'-dibutyryl-adenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP), and elevated potassium were also inhibited by ANF. Inhibition could be partially overcome by high doses of agonist. Inhibition was localized to the early pathway of aldosteronogenesis, to a step before cholesterol side-chain cleavage. ANF had no effect on binding of AII to receptors, on the stimulation by AII of phospholipid turnover, or on the alteration by AII of calcium fluxes.

Adrenal Glands↗
PubMed1984

Hormonal and metabolic effects of angiotensin converting enzyme inhibitors. Possible differences between enalapril and captopril.

Inhibitors of angiotensin converting enzyme block the conversion of angiotensin I to angiotensin II, the active hormone of the renin-angiotensin system. This inhibition leads to a reduction in angiotensin-mediated vasoconstriction and aldosterone production. Although converting enzyme inhibitors have other potential metabolic effects, their beneficial effects in hypertension and congestive heart failure appear to be, in large part, related to their ability to reduce angiotensin II. This causes an increase in plasma renin levels and a fall in plasma and urine aldosterone, which can be sustained for many years. As a consequence, converting enzyme inhibitors produce mild natriuresis and positive potassium balance. At conventionally used doses, enalapril more completely prevents posture-induced increases in aldosterone than does captopril, probably reflecting more complete inhibition of angiotensin II formation in vivo.

Aldosterone↗
PubMed1984

Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the renin-aldosterone system in dogs.

Auriculin is a potent vasoactive and natriuretic peptide that was recently isolated and purified from rat atrial tissue. Since this peptide could be of great importance for renal, cardiovascular, and volume homeostasis, its functional properties have been characterized in dogs. The effects of synthetic auriculin on renal function, mean blood pressure, plasma renin activity, renin secretory rate, and plasma aldosterone levels were determined. Auriculin was administered intravenously as a prime (1.0 microgram/kg body weight) and constant infusion (0.1 microgram per minute/kg body weight for one hour) to five anesthetized dogs. In addition, two conscious dogs were used to verify some of the results obtained in anesthetized dogs. Auriculin decreased mean blood pressure from 134 +/- 5 to 122 +/- 4 mm Hg (p less than 0.05, paired t test) and increased glomerular filtration rate (25.5 +/- 2.7 to 32.4 +/- 4.1 ml per minute per kidney, p less than 0.05), diuresis (0.21 +/- 0.03 to 1.06 +/- 0.14 ml per minute per kidney, p less than 0.05), natriuresis (38 +/- 0.6 to 187 +/- 35 mueq per minute per kidney, p less than 0.05), and kaliuresis (14.8 +/- 1.6 to 35.7 +/- 6.3 mueq per minute per kidney, p less than 0.05). These effects were sustained throughout the infusion of auriculin and were entirely reversible. Renal plasma flow increased transiently for one to two minutes, and then returned to or below control levels. Urine osmolality decreased by 40 percent (p less than 0.05) whereas free water clearance remained unchanged (p less than 0.05). Auriculin reversibly decreased plasma renin activity (11.6 +/- 2.3 to 3.6 +/- 1.2 ng/ml per hour, p less than 0.05), renin secretory rate (895 +/- 313 to 255 +/- 28 ng per hour per minute, p less than 0.05), and plasma aldosterone levels (8.4 +/- 1.6 to 3.6 +/- 0.7 ng/dl, p less than 0.05), whereas plasma cortisol levels remained unchanged. These results demonstrate that auriculin has a unique combination of functional properties, increasing glomerular filtration rate, diuresis, and natriuresis, without a sustained increase in total renal blood flow, and lowering blood pressure, plasma renin levels, renin secretory rate, and plasma aldosterone levels. These properties suggest an important potential role for atrial natriuretic peptides in the regulation of renal function, extracellular volume, and blood pressure.

Aldosterone↗
PubMed1984

Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney.

The effects of rat atrial tissue extract on renal hemodynamics and fluid and electrolyte excretion were investigated in the isolated perfused rat kidney (IK). IK were perfused at a constant effective perfusion pressure of about 90 mmHg. After control clearance periods (C), extracts of rat atria (AE) or ventricles (VE) were added to the perfusate and three 10-min experimental periods followed. AE, but not VE, significantly increased (P less than 0.001) renal vascular resistance (RVR) to 133 +/- 8% of C, GFR to 201 +/- 34%, filtration fraction to 245 +/- 41%, urine flow (V) to 675 +/- 131%, fractional excretion (FE) of H2O to 336 +/- 29%, absolute Na excretion (UNaV) to 1,259 +/- 290%, FENa to 642 +/- 129%, UKV to 2,226 +/- 1,237%, and FEK to 542 +/- 119%. Despite the marked natriuresis, since GFR doubled, Na reabsorption rose from 78.3 +/- 36.3 in C to 132 +/- 36.3 mueq/min after AE. The effects of AE were immediate and lasted to the end of the perfusion. The lower the initial control GFR, the larger was the AE-induced increase in GFR. Perfusion with low [Ca] (0.2 mM) or verapamil (10(-5) M) severely blunted the hemodynamic, diuretic, kaliuretic, and natriuretic effects of AE. AE decreased rather than increased the RVR when IK were perfused with vasoconstrictors such as angiotensin II, norepinephrine, or vasopressin. The results demonstrate that AE acts directly on the kidney, eliciting powerful Ca-dependent hemodynamic and natriuretic responses. The natriuresis induced by AE can be accounted for, at least in part, by its renal hemodynamic effects rather than by the presence of a putative tubular natriuretic factor. The hypothesis is advanced that AE contains a substance(s) which behaves as a functional agonist/antagonist of endogenous vasoconstrictors with a preferential site of action on the efferent arterioles of the renal vasculature.

Animals↗
PubMed1984

Characterization of inactive renin ("prorenin") from renin-secreting tumors of nonrenal origin. Similarity to inactive renin from kidney and normal plasma.

Inactive renin comprises well over half the total renin in normal human plasma. There is a direct relationship between active and inactive renin levels in normal and hypertensive populations, but the proportion of inactive renin varies inversely with the active renin level; as much as 98% of plasma renin is inactive in patients with low renin, whereas the proportion is consistently lower (usually 20-60%) in high-renin states. Two hypertensive patients with proven renin-secreting carcinomas of non-renal origin (pancreas and ovary) had high plasma active renin (119 and 138 ng/h per ml) and the highest inactive renin levels we have ever observed (5,200 and 14,300 ng/h per ml; normal range 3-50). The proportion of inactive renin (98-99%) far exceeded that found in other patients with high active renin levels. A third hypertensive patient with a probable renin-secreting ovarian carcinoma exhibited a similar pattern. Inactive renins isolated from plasma and tumors of these patients were biochemically similar to semipurified inactive renins from normal plasma or cadaver kidney. All were bound by Cibacron Blue-agarose, were not retained by pepstatin-Sepharose, and had greater apparent molecular weights (Mr) than the corresponding active forms. Plasma and tumor inactive renins from the three patients were similar in size (Mr 52,000-54,000), whereas normal plasma inactive renin had a slightly larger Mr than that from kidney (56,000 vs. 50,000). Inactive renin from each source was activated irreversibly by trypsin and reversibly by dialysis to pH 3.3 at 4 degrees C; the reversal process followed the kinetics of a first-order reaction in each instance. The trypsin-activated inactive renins were all identical to semipurified active renal renin in terms of pH optimum (pH 5.5-6.0) and kinetics with homologous angiotensinogen (Michaelis constants, 0.8-1.3 microM) and inhibition by pepstatin or by serial dilutions of renin-specific antibody. These results indicate that a markedly elevated plasma inactive renin level distinguishes patients with ectopic renin production from other high-renin hypertensive states. The co-production of inactive and active renin by extrarenal neoplasms provides strong presumptive evidence that inactive renin is a biosynthetic precursor of active renin. The unusually high proportion of inactive renin in plasma and tumor extracts from such patients is consistent with ineffective precursor processing by neoplastic tissue, suggesting that if activation of "prorenin" is involved in the normal regulation of active renin levels it more likely occurs in the tissue of origin (e.g., kidney) than in the circulation.

Adult↗
PubMed1984

Antihypertensive and aldosterone-lowering effects of synthetic atrial natriuretic factor in renin-dependent renovascular hypertension.

A 24-amino acid residue synthetic atrial natriuretic factor (ANF) antagonizes angiotensin II-induced vascular contractility and aldosterone production in isolated blood vessels and adrenal cells, respectively. To determine the significance of these effects in vivo, the blood pressure and aldosterone responses to synthetic ANF were evaluated in rats with two-kidney, one clip hypertension (n = 5) and in sham-operated controls (n = 4). In the latter, ANF caused a slight fall in mean blood pressure (-7 +/- 3%) and inconsistent changes in plasma renin and aldosterone. In hypertensive rats, ANF decreased blood pressure by 31 +/- 7 mmHg (17 +/- 3%), comparable to the effect of the angiotensin antagonist saralasin (31 +/- 4 mmHg). Plasma renin activity increased from 48 +/- 15 to 79 +/- 23 ng/ml/h. Despite this, ANF caused marked suppression of plasma aldosterone (from 97 +/- 28 to 20 +/- 8.9 ng/100 ml). These results show that ANF can exert potent antihypertensive and aldosterone-lowering effects in vivo, at least when the renin-angiotensin system is stimulated.

Aldosterone↗