Biomedical subjects

J H Laragh

Publications and source records attributed to J H Laragh.

At least 127 records · Page 7Linked to original sources

PubMed1991

Characterization of auscultatory gaps with wideband external pulse recording.

Three types of auscultatory gaps, called G1, G2, and G3, that occur during blood pressure measurement have been identified by using wideband external pulse recording. We have previously shown that the wideband external pulse recorded during cuff deflation can be separated into three components (K1, K2, and K3), one of which (K2) is closely related to the Korotkoff sound. G1 occurs with cuff pressure just below systolic and is characterized by the presence of K1 and K2 with intermittent disappearance of K2. G1 gaps are related to a phasic decrease of arterial (systolic) pressure and were exhibited by 13 of 60 hypertensive patients. G2 gaps are related to a phasic increase of arterial (diastolic) pressure, occur when cuff pressure is just above diastolic, and are characterized by the presence of K1, K2, and K3 with intermittent disappearance of K2. Seven of 60 hypertensive patients exhibited a G2 gap. G3 gaps occur with cuff pressure between systolic and diastolic and are characterized by an underdeveloped or blunted K2 signal. Three of 60 hypertensive patients exhibited a G3 gap. The identification of auscultatory gaps in relation to the wideband external pulse provides a qualitative measure of their existence, can be of significant value in better understanding aspects of the auscultatory blood pressure measurement technique, and provides an objective basis with which to better understand the mechanisms that cause them.

Auscultation↗

PubMed1991

Cellular ions in hypertension, diabetes, and obesity. A nuclear magnetic resonance spectroscopic study.

To investigate the cellular basis linking hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and obesity, we used 31P and 19F nuclear magnetic resonance spectroscopy to measure intracellular pH (pHi), free magnesium (Mgi), and cytosolic free calcium (Cai) in erythrocytes of obese and NIDDM subjects with and without hypertension. Compared with normotensive, nondiabetic controls (Cai, 25.2 +/- 1.4 nM; Mgi, 232 +/- 8 microM), Cai was elevated in both normotensive (36.8 +/- 2.7 nM, sig = 0.005) and hypertensive (43.4 +/- 2.9 nM, sig = 0.001) NIDDM subjects, and Mgi was concomitantly suppressed (normotensive: 206 +/- 11 microM, sig = 0.05; hypertensive: 196 +/- 8 microM, sig = 0.001). Similar but less striking changes were noted in obese subjects. Values of pHi were significantly lower (sig = 0.05) in all hypertensive groups compared with their normotensive controls. Continuous relations were observed for all subjects between Cai and diastolic blood pressure (r = 0.649, p less than 0.001) and body mass index (r = 0.565, p less than 0.001), between Mgi and diastolic blood pressure (r = -0.563, p less than 0.001) and fasting blood glucose (r = -0.580, p less than 0.001), and in diabetics, between pHi and diastolic blood pressure (r = -0.680, p less than 0.001). Thus, the constellation of elevated Cai and suppressed Mgi and pHi levels is characteristic of the hypertensive state. These abnormalities of cellular ion handling in whole or in part common to hypertension, diabetes, and obesity may contribute to the pathophysiology of these syndromes and may help to explain their frequent clinical coexistence.

Calcium↗

PubMed1991

Abnormal sodium metabolism and plasma renin activity (renal renin secretion) and the vasoconstriction volume hypothesis: implications for pathogenesis and treatment of hypertension and its vascular consequences (heart attack, stroke).

Arterial hypertension is sustained by either of two long-term mechanisms of arteriolar vasoconstriction or by an inappropriate reaction between them. One mechanism is renin-mediated, the other is related to antecedent renal sodium retention. The plasma renin value directly reflects the presence and degree of renin-mediated vasoconstriction, and, inversely, defines the predominance of sodium-related vasoconstriction. A hypotensive response, or lack of it, to angiotensin-converting enzyme inhibitor is similarly informative. Because the normal kidney exposed to high arterial pressure and normal salt intake will reduce its renin secretion to near zero, any renin secretion in a hypertensive setting can be considered abnormal. Typically, high-renin hypertensive patients are more vasoconstricted than low-renin patients with similar blood pressures. The intense vasoconstriction leads to relative hypovolemia, hemoconcentration, hyperviscosity, postural hypotension, and in severe forms even to acrocyanosis, all of which are dramatically reversed with anti-renin therapy. Conversely, low-renin equally hypertensive patients have relatively more sodium volume and are less vasoconstricted; they are generally responsive to natriuretic drugs (e.g., diuretics or calcium antagonists) and appear relatively protected from vascular sequelae such as stroke and heart attack. These observations provide a new means for evaluating prognosis and a basis for mechanistically differentiating and treating hypertensive patients, allowing increasingly simpler and more-specific long-term therapies.

Animals↗

PubMed1991

Clinical evaluation and differential diagnosis of the individual hypertensive patient.

This paper attempts to define the theory and practice of a modern approach to the initial workup of the patient with hypertension. The process includes a complete general medical evaluation along with special measures to enable the fullest characterization and clinical differentiation of the disease. The initial workup aims to (a) establish that the hypertension is sustained and should be treated; (b) identify all definable and curable causes for the hypertension; (c) identify the presence and degree of attendant risk factors such as smoking, alcohol use, obesity, diabetes, and abnormal lipid metabolism; (d) characterize the hypertension in terms of its pathophysiology; and (e) assess the presence and degree of target organ damage to the heart, brain, and kidneys. Because all diastolic hypertension is due to arteriolar vasoconstriction, a fundamental strategy of this process is to distinguish between renin-mediated and sodium-related vasoconstrictive forces and to evaluate which is preponderant. The chief instruments of this strategy are the renin-sodium profile and the response of plasma renin activity and blood pressure to specific antirenin system drugs. The captopril test, an important protocol in making this distinction, is primarily a powerful screening tool for confirming the possible presence or absence of curable renovascular disease or curable primary aldosteronism. That renin profiling cannot accurately discriminate between the contributions of either the renin or sodium-volume factors in that large fraction of medium-renin patients is not a viable reason for not performing the test. The test has its greatest strength for identifying sizable numbers of otherwise unrecognizable patients with very high or very low renin concentrations who might have curable disorders and who likely reflect different pathophysiologic vasoconstrictive mechanisms for which entirely different drug therapies are appropriate. However, the baseline renin test is also useful for assessing prognosis and the likelihood of a heart attack and it is valuable for deciding whether to use an anti-renin system drug (for medium and high renin concentrations) as opposed to natriuretic agents (low-renin patients) such as a diuretic or calcium antagonists as the primary step. In our present state of knowledge, the basic diagnostic biochemical workup includes the renin-sodium profile and the 24-h urinary sodium, potassium, and microalbumin excretion rates. This package is further enriched by baseline electrocardiography and echocardiography and the evaluation of glucose and lipid patterns.(ABSTRACT TRUNCATED AT 400 WORDS)

Antihypertensive Agents↗

PubMed1991

Discordant nephron function. A pathogenic factor in hypertension and its vascular complications of stroke and heart attack.

Morphologic evidence from patients with essential hypertension and Goldblatt-type hypertension reveals a subpopulation of narrowed afferent arterioles to ischemic nephrons. These ischemic nephrons, responding individually to their perception of underperfusion, secrete renin. In response, the normal nephrons are in adaptive natriuresis and have appropriately shut off their renin production. Nevertheless, they are affected adversely by the discordant renin-angiotensin II arising from the ischemic nephrons' presence, which exerts an unwanted sodium-retaining effect on the proximal tubules of the adapting nephrons. The end result is elevated blood pressure from too much sodium retention for the level of renin activity, that is, an abnormal renin-sodium product. Thus, "normal" renin levels in a hypertensive individual are abnormal because healthy kidneys shut off renin production entirely when blood pressure rises. This construction explains why angiotensin converting enzyme inhibition often corrects "normal" renin hypertension. Although such hypertension may be partly sodium-mediated as a consequence of inappropriate sodium retention by the normal and ischemic nephrons, the source of the problem lies in the renin production from ischemic nephrons. The correct treatment, then, is an antirenin therapy designed to block renin synthesis or secretion or angiotensin II formation or action. In view of modern studies suggesting that renin excesses also correlate with an increased risk of heart attack and stroke, the role of antirenin and antiangiotensin agents in treatment assumes additional relevance.

Blood Pressure↗

PubMed1990

Relation of obesity, high sodium intake, and eccentric left ventricular hypertrophy to left ventricular exercise dysfunction in essential hypertension.

PURPOSE: To elucidate determinants of abnormal left ventricular functional responses to exercise in hypertensive patients. PATIENTS AND METHODS: One hundred twenty-seven patients with uncomplicated essential hypertension were studied by rest and exercise radionuclide angiography and by echocardiography at rest. RESULTS: The 24 patients with subnormal left ventricular ejection fraction at peak exercise (less than 54%) were similar in age and rest and exercise blood pressures to the 103 with normal exercise ejection fraction, but were more obese (p less than 0.005) and had greater left ventricular mass (p less than 0.03) and internal dimensions (p less than 0.001). The parallel increase in left ventricular chamber size and mass (eccentric hypertrophy) in the group of patients with exercise dysfunction was associated with higher resting end-systolic wall stress (p less than 0.001) and abnormal increases of end-systolic left ventricular volume from rest to peak exercise (p less than 0.001). Multivariate analysis revealed that exercise left ventricular dysfunction was independently associated with higher left ventricular mass (p less than 0.0005), end-systolic wall stress (p less than 0.001), dietary sodium intake (p less than 0.01), and body mass index (p less than 0.03). CONCLUSION: Among patients with uncomplicated essential hypertension, abnormal functional responses to exercise are strongly associated with eccentric ventricular hypertrophy, obesity, and high sodium intake.

Cardiomegaly↗

PubMed1990

Longitudinal study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: deviations related to the development of superimposed preeclampsia.

A prospective longitudinal study of 25 pregnant women (30 pregnancies) with chronic hypertension, a group prone to development of preeclampsia, was conducted to explore the relationship between the renin-angiotensin-aldosterone system and the development of superimposed preeclampsia. In women with chronic hypertension in whom preeclampsia did not develop (17 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated, beginning in the first trimester and continuing throughout pregnancy as found previously in normotensive pregnant women (n = 58). Plasma estradiol and progesterone levels also increased progressively. In women with chronic hypertension in whom preeclampsia developed (13 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated in the first trimester as in the other groups. However, later in pregnancy significant differences were observed. Blood pressure began to rise in the second trimester. Initially the renin-angiotensin-aldosterone system remained stimulated, but in the early third trimester, when preeclampsia was diagnosed, plasma renin activity and urine aldosterone excretion decreased, and atrial natriuretic factor increased. These data provide information that may be useful in the recognition of superimposed preeclampsia, and in the investigation of its pathogenesis.

Adult↗

PubMed1990

Diurnal and postural variations in plasma atrial natriuretic factor, plasma guanosine 3':5'-cyclic monophosphate and sodium excretion.

1. We studied diurnal patterns of plasma atrial natriuretic factor, plasma guanosine 3':5'-cyclic monophosphate and urinary sodium excretion in normal subjects after 3 days on a 200 mmol of sodium/60 mmol of potassium diet. On the fourth day blood samples and urine were collected every 3 h. 2. Two studies were performed. In study 1, normal subjects (n = 8) were recumbent for 23 h from 09.00 hours to 08.00 hours the next day. In study 2, normal subjects (n = 10) were permitted to ambulate from 09.00 hours to 23.00 hours and then were recumbent until 08.00 hours the next day. 3. In study 1, assumption of the recumbent posture was associated with increases in plasma atrial natriuretic factor (P less than 0.01), plasma guanosine 3':5'-cyclic monophosphate (P less than 0.05) and urinary sodium excretion (P less than 0.05). 4. In contrast, in study 2 there were no significant changes in plasma atrial natriuretic factor during the day; instead, plasma atrial natriuretic factor increased overnight, reaching a peak at 24.00 hours after 1 h of recumbency (P less than 0.01). A smaller rise in plasma guanosine 3':5'-cyclic monophosphate (P less than 0.05) occurred; urinary sodium excretion decreased markedly (P less than 0.01) and there was no change in creatinine clearance. 5. In both studies, recumbency was associated with an initial drop, followed by a rise, in packed cell volume. 6. These data demonstrate that assumption of the supine position induces a rise in plasma atrial natriuretic factor and accounts for most of the observed variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

New angiotensin converting enzyme inhibitors. Their role in the management of hypertension.

The introduction of orally active angiotensin converting enzyme (ACE) inhibitors has revolutionized the treatment of hypertensive disorders and provided an effective alternative for the management of congestive heart failure (CHF). By interfering with the formation of angiotensin II, the active agent of the renin system, ACE inhibitors block the system's vasoconstrictive and sodium-retaining effects, with a consequent reduction in systemic blood pressure. The net effect is improved blood flow and reduced cardiac work. Thus, ACE inhibitors are likely to improve cardiac work capacity and quality of life. Their mechanism of action differs markedly from that of traditional antihypertensive agents which lower blood pressure while reducing cardiac output and blood flow. Since the primary action of ACE inhibitors is to block the renin system, a dramatic response to monotherapy suggests a large renin factor while the lack of a response suggests a low-renin state more amenable to treatment with a diuretic or calcium antagonist. Because of their many attributes, ACE inhibitors are increasingly used as first-line therapy for the treatment of hypertension or CHF. The prototype orally active ACE inhibitor, captopril, is a sulfhydryl compound with a good safety profile at the recommended dosages but reported toxicity at higher dosages. Second-generation ACE inhibitors (eg, enalapril and quinapril) are more potent sulfhydryl-free esters with a greater affinity for the converting enzyme. These newer agents are pro-drugs requiring ester hydrolysis to form the active free acid compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1990

Infusion of recombinant human prorenin into rhesus monkeys. Effects on hemodynamics, renin-angiotensin-aldosterone axis and plasma testosterone.

Prorenin, the biosynthetic precursor of active renin, is present in high concentrations in the kidney and reproductive organs. We have proposed that prorenin may be the vehicle of local renin systems, separating the functions of circulating and tissue renin. In the present study, we investigated the effect of increasing plasma prorenin 3- to 4-fold by infusing recombinant prorenin, 400 ng/min for 40 min, into male rhesus monkeys. The prorenin was first warmed to 37 degrees C to reduce the endogenous renin activity to a minimum. The study included a 20 min baseline and a 40 min recovery period. Plasma prorenin increased from 72 +/- 14 ng/mL/h to a maximum of 246 +/- 18 ng/mL/h during the infusion (P less than .001) and fell to 169 +/- 23 ng/mL/h 40 min after the infusion was stopped. Active renin did not change significantly. Plasma aldosterone increased slightly during the prorenin infusion (by 13%) and returned to baseline during the recovery period (P less than .05 compared to the infusion period). Plasma testosterone fell significantly from 1.9 +/- 0.1 ng/mL to 1.6 +/- 0.1 ng/mL during the infusion and further to 1.4 +/- 0.1 ng/mL during the post-infusion period (P less than .05). Blood pressure fell slightly but not significantly. Heart rate, glomerular filtration rate and renal blood flow, as well as urine flow and urine sodium and potassium excretion showed no significant change. These results demonstrate that human recombinant prorenin is not converted to active renin in the circulation of rhesus monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗

PubMed1990

Hypertension and peripheral insulin resistance. Possible mediating role of intracellular free magnesium.

To investigate the association of hypertension and insulin resistance, we utilized 31P-NMR spectroscopy to noninvasively assess intracellular free magnesium levels (Mgif) in erythrocytes of normotensive (n = 20) and essential hypertensive (n = 20) subjects given an oral 100 g glucose load. In hypertensive compared with normotensive subjects, fasting glucose and insulin levels were similar, but the integrated insulinemic responses to glucose were 45% greater (312 +/- 13.4 v 215 +/- 7.5 microU/mL, P less than .001). In hypertension, Mgif levels were significantly reduced (183 +/- 9 v 251 +/- 9 mumol/L, P less than .001), and for all subjects were closely and inversely related to systolic (r = -0.77, P less than .001) and diastolic (r = -0.81, P less than .001) blood pressures, and to the integrated insulin response (r = -0.72, P less than .001). Furthermore, while insulin responses were also related to the underlying systolic (r = 0.69, P less than .001) and diastolic (r = .73, P less than .001) pressures, these relations were no longer significant when adjusted for Mgif levels. We hypothesize that hypertension and peripheral insulin resistance may be different clinical expressions of a common abnormal intracellular ionic environment, characterized at least in part by suppressed levels of intracellular free magnesium.

Erythrocytes↗

PubMed1990

A new circulating hypertensive factor in the plasma of essential hypertensive subjects.

The pressor responses to dialyzed plasma extracts from normotensive (n = 15) and essential hypertensive (n = 14) human subjects were evaluated in anesthetized Sprague-Dawley rats. Hypertensive but not normotensive plasma raised mean arterial pressure (23.6 +/- 3.6 versus -0.5 +/- 2.5 mmHg, P less than 0.0001), and this effect was correlated significantly with its ability to stimulate 45Ca uptake in rat tail artery vascular smooth muscle (r = 0.883, P less than 0.002). These data suggest a humoral contribution to the pathophysiology of essential hypertension in at least some individuals. The time-course and molecular weight distribution of the dialyzed plasma suggest that this effect is not due to known vasopressor substances, but to a factor we tentatively term plasma hypertensive factor.

Animals↗

PubMed1990

Relation of blood viscosity to demographic and physiologic variables and to cardiovascular risk factors in apparently normal adults.

Although increased blood viscosity occurs in several cardiovascular diseases, little is known of factors influencing blood rheology in normal adults. Accordingly, we examined the relations of whole blood viscosity (WBV) to its rheologic determinants (hematocrit level, plasma viscosity, protein concentration, and red cell aggregability and rigidity), to demographic and laboratory variables, and to cardiovascular risk factors in 128 normotensive employed adults. Hematocrit levels accounted for 67-84% of variability of WBV at shear rates from 208 to 0.1 sec-1 with lesser contributions from plasma viscosity, red cell aggregability, and rigidity (multiple r = 0.95-0.97); WBV was predicted accurately from standard measurements of hematocrit and total plasma protein levels (multiple r = 0.78-0.92 in "learning" and "test" analysis). Male sex, obesity, dietary Na+ intake, and increasing age had additive effects on WBV (multiple r greater than or equal to 0.59, p less than 0.00001); the last three of these factors and black race independently predicted plasma viscosity (multiple r = 0.36, p less than 0.001). Among regulators of plasma volume, plasma renin activity and urinary Na+ excretion bore independent positive relations to WBV. Diastolic and mean blood pressures were independent predictors of WBV and hematocrit levels (all p less than 0.05). Conventional risk factors (e.g., triglycerides, obesity, and cholesterol levels) were positively related to WBV or plasma viscosity. Thus, in apparently normal adults, 1) WBV or plasma viscosity are increased by male sex, obesity, high sodium intake, aging, and black race, 2) WBV is positively related to plasma renin activity, 3) WBV or plasma viscosity are related to diastolic and mean blood pressures, triglycerides and cholesterol concentrations, and 4) WBV can be predicted from simple measurements of hematocrit and total plasma protein levels.

Adult↗

PubMed1990

Relation of left ventricular hemodynamic load and contractile performance to left ventricular mass in hypertension.

The weak relation of systolic blood pressure to left ventricular mass in hypertensive patients is often interpreted as evidence of nonhemodynamic stimuli to muscle growth. To test the hypothesis that left ventricular chamber size, reflecting hemodynamic volume load and myocardial contractility, influences the development of left ventricular hypertrophy in hypertension, we studied actual and theoretic relations of left ventricular mass to left ventricular diastolic chamber volume, pressure and volume load, and an index of contractility. Data were obtained from independently measured M-mode and two-dimensional echocardiograms in 50 normal subjects and 50 untreated patients with essential hypertension. Two indices of overall left ventricular load were assessed: total load (systolic blood pressure x left ventricular endocardial surface area) and peak meridional force (systolic blood pressure x left ventricular cross sectional area). A theoretically optimal left ventricular mass, allowing each subject to achieve mean normal peak stress, was calculated as a function of systolic blood pressure and M-mode left ventricular end-diastolic diameter. Left ventricular mass measured by M-mode echo correlated better with two-dimensional echocardiogram derived left ventricular end-diastolic volume (r = 0.56, p less than 0.001) than with systolic blood pressure (r = 0.45, p less than 0.001) and best with total load or peak meridional force (r = 0.68 and 0.70, p less than 0.001). In multivariate analysis both end-diastolic volume and blood pressure were independent predictors of systolic mass (p less than 0.001) and explained most of its variability (R = 0.75, p less than 0.001). Theoretically optimal left ventricular mass was more closely related to end-diastolic volume (r = 0.72, p less than 0.001) than to systolic blood pressure (r = 0.46, p less than 0.001); thus, the relatively weak correlation between blood pressure and optimal mass reflected the influence of left ventricular cavity size, rather than a lack of proportionality between load and hypertrophy. Actual and theoretically optimal left ventricular mass were closely related (r = 0.76, p less than 0.001), indicating that left ventricular hypertrophy in most cases paralleled hemodynamic load. Left ventricular mass was positively related to stroke index and inversely to contractility (as estimated by the end-systolic stress/volume index ratio), the main determinants of left ventricular chamber volume. In multivariate analysis, systolic blood pressure, stroke index, and the end-systolic stress/volume index ratio were each independently related to left ventricular mass index (all p less than 0.001, multiple R = 0.81) and accounted for 66% of its overall variability.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1990

Relation of plasma renin to end organ damage and to protection of K+ feeding in stroke-prone hypertensive rats.

We studied the effects of regular diet (0.35% NaCl/1.1% potassium), high sodium diet (4% NaCl/0.75% potassium), or high sodium and high potassium diet (4% NaCl/2.11% potassium) on blood pressure, plasma renin activity, renal and cerebrovascular lesions, and incidence of stroke and mortality in male stroke-prone spontaneously hypertensive rats (SHRSP). In the first 4 weeks, the rise in blood pressure was higher in high NaCl than in high NaCl/high potassium or regular diet groups. However, by 8 and 12 weeks, the blood pressure in all three groups was similar. After 4 weeks of diet, plasma renin activity was similar in the three groups (3.4 +/- 0.8, 4.1 +/- 0.9, and 5.2 +/- 1.6 ng/ml/hr, in high NaCl, high NaCl/high potassium, and regular diet groups, respectively) and were not related to sodium excretion. After 8 weeks, plasma renin activity was significantly increased only in the high NaCl group (13.7 +/- 3.7 ng/ml/hr), and by 12 weeks plasma renin activity was significantly higher in the high NaCl group (25.3 +/- 3.6 ng/ml/hr) than in the high NaCl/high potassium (11.1 +/- 2.9 ng/ml/hr) or in the regular diet (7.8 +/- 4.6 ng/ml/hr) groups. Moderate to severe renal vascular lesions were first detected in the high NaCl group by 8 weeks of diet. At 12 weeks, renal vascular damage index (RVDI), estimated histologically, was significantly higher in the high NaCl group (RVDI = 79 +/- 14) than in the high NaCl/high potassium (RVDI = 40 +/- 11) and regular diet (RVDI = 7.8 +/- 4.6) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Angiotensin II-induced atrial natriuretic factor release in dogs is not related to hemodynamic responses.

Angiotensin II (Ang II) and atrial natriuretic factor (ANF) appear to act as functional antagonists in the regulation of fluid and electrolyte homeostasis and blood pressure. To further define the relations between these hormones in vivo, we investigated the effect of low doses of Ang II (1-10 ng/kg/min) on plasma ANF levels. We also evaluated the influence of ANF release on the renal and hormonal responses to ANG II. Studies were performed in anesthetized and conscious instrumented dogs during sustained saline load and converting enzyme inhibition. In the anesthetized dogs, Ang II significantly increased plasma ANF levels and ANF arteriovenous difference without changing either atrial pressures or hematocrit. In both conscious and anesthetized dogs, ANF increases were not correlated with blood pressure responses to Ang II and did not occur in control groups when Ang II was replaced by vehicle. Ang II-induced sodium retention and stimulation of aldosterone production were attenuated, and renin suppression was enhanced in dogs having the largest changes in plasma ANF in response to converting enzyme inhibition or Ang II. These results demonstrate that in volume-replete dogs Ang II can promote ANF release independently of changes in atrial pressures or systemic hemodynamics, suggesting that Ang II may exert a significant modulatory effect on ANF secretion. The results also show significant relations between ANF and renal and adrenal responses to Ang II, which may suggest that, in turn, endogenous ANF modulates the effects of Ang II.

Adrenal Glands↗

PubMed1990

Role of the kidney in congestive heart failure. Relationship of cardiac index to kidney function.

Because of inappropriate signals from the volume-regulation system and a reduction in renal blood flow, the kidney is not able to prevent sodium and water retention in chronic congestive heart failure (CHF). A brief summary of normal renal function and renal involvement in CHF is given and a study of renal function in patients with moderate or severe chronic CHF is presented. To evaluate the impact of cardiac output reduction on the regulation of the glomerular filtration rate (GFR) in heart failure, GFR (inulin clearance), renal plasma flow [p-aminohippurate (PAH) clearance], invasive haemodynamics, blood volume, plasma renin and plasma catecholamines were measured in 34 patients with chronic CHF. The patients were divided into 3 groups according to their cardiac index (CI): CI greater than 2.0 L/min/m2 (group A), CI 1.5 to 2.0 L/min/m2 (group B), and CI less than 1.5 L/min/m2 (group C). Differences in the relationship between GFR, renal plasma flow and filtration fraction for the 3 groups emerged. Despite an intergroup reduction in the renal fraction of cardiac output and renal blood flow, GFR was similar in groups A and B (62 and 67 ml/min/1.73 m2, respectively), and was accompanied by a compensatory increase in filtration fraction, from 24% in group A to 35% in group B. Group C had a much lower GFR (38 ml/min/1.73 m2), however, the filtration fraction (28%) was intermediate in value between those of groups A and B. The differences in GFR were reflected by blood urea nitrogen levels but not by serum creatinine levels. The occurrence of a non-compensatory filtration fraction response in the patients with the greatest impairment of CI and renal blood flow suggests that GFR becomes dependent on afferent arteriolar flow in the most severe heart failure, despite stimulation of haemodynamic and hormonal pathways, which would normally increase efferent arteriolar tone. It is thus suggested that GFR becomes flow dependent in patients in the most severe stage of chronic CHF.

Adult↗

PubMed1989

Nephron heterogeneity: clue to the pathogenesis of essential hypertension and effectiveness of angiotensin-converting enzyme inhibitor treatment.

It is proposed that in essential hypertension there are two functionally abnormal populations of nephrons. One is ischemic; chronically hypersecreting renin and underexcreting sodium. The other, the larger population, is in adaptive hypernatriuresis with its renin secretion chronically suppressed. Nephrons in these two populations, each with its own detector-effector apparatus for renin secretion and sodium excretion, behave according to their individual needs, producing a physiologic discordance expressed in high blood pressure even with plasma renin levels in the so-called "normal" range. The unsuppressed and inappropriate renin secretion from the ischemic nephrons impairs renal function in ischemic and hyperfiltering nephrons alike, but in very different ways. To maintain glomerular filtration rate and an adequate excretion of sodium, the ischemic nephrons require a higher rate of renin secretion than they are actually receiving, because at low perfusion pressures maximal angiotensin II-induced efferent arteriolar constriction is needed to maintain glomerular filtration rate. On the other hand, the compensating hypernatriuretic nephrons become unable fully to excrete dietary sodium because they are exposed to an unwanted, inappropriately high angiotensin II level coming from the ischemic nephrons. This angiotensin II impairs sodium excretion (adaptive hypernatriuresis) from unaffected, adapting nephrons by promoting proximal sodium reabsorption and by inducing afferent constriction. The net result is that all nephrons are exposed to angiotensin II levels inappropriate for their needs. This leads to impaired ability to excrete sodium by both populations of nephrons, with sodium retention in the presence of abnormal renin secretion and perpetuation of the hypertension. The hypothesis is consistent with the hallmark pathology of multifocal afferent arteriolar narrowing seen in essential hypertension as well as with the characteristic renal hemodynamic pattern of vasoconstriction with reduced renal blood flow but with maintained glomerular filtration rate. The "normal" glomerular filtration rate as well as the often "normal" plasma renin activity may be seen as the sum of effects on the two abnormally acting populations of nephrons. Further, since any circulating renin is inappropriate in the presence of hypertension, the hypothesis helps explain why angiotensin-converting enzyme inhibitors reduce blood pressure even when renin levels are not elevated.

Angiotensin-Converting Enzyme Inhibitors↗