Biomedical subjects

M W Brands

Publications and source records attributed to M W Brands.

At least 55 records · Page 3Linked to original sources

PubMed1994

Long-term cardiovascular role of nitric oxide in conscious rats.

The goal of this study was to determine the arterial pressure and renal excretory responses to a continuous intravenous infusion of 7.4 nmol/kg per minute of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in conscious rats. Studies were conducted in six groups of Sprague-Dawley rats with indwelling arterial and venous catheters over periods lasting 12 to 26 days. In the first group of rats, L-NAME infusion for 9 days caused a sustained increase in arterial pressure, and on the ninth day arterial pressure was increased 29 mm Hg. Infusion of L-NAME at the higher dose of 37 nmol/kg per minute for 9 days caused no greater increase in arterial pressure than the lower dose. Sodium and volume balances and phenylephrine pressor sensitivity were unchanged during L-NAME administration at 7.4 nmol/kg per minute; plasma renin activity increased 2.5-fold, but the vasodepressor and vasodilator responses to acetylcholine and bradykinin were unchanged. Arterial pressure remained significantly increased 7 days after L-NAME was stopped, but in another group of rats, intravenous L-arginine infusion caused arterial pressure to return to control within 1 day. This same dose of L-arginine was administered for 7 days intravenously, and neither arterial pressure nor sodium balance changed. In other groups of rats, L-arginine was administered in conjunction with L-NAME; this prevented any change in arterial pressure, whereas D-arginine did not. In conclusion, the data suggest that continuous intravenous infusion of L-NAME causes sustained increases in arterial pressure in conscious rats without any sodium or water retention. The hypertension is accompanied by increases in plasma renin activity and can be prevented with intravenous L-arginine administration.

Animals↗

PubMed1993

Chronic angiotensin-converting-enzyme inhibition improves cardiac output and fluid balance during heart failure.

The purpose of this study was to examine the sequential changes in renal and cardiovascular function produced by chronic Benazepril administration at different stages of heart failure in dogs. Heart failure was produced by rapid ventricular pacing in five dogs with a normally functioning renin-angiotensin system (angiotensin normal, AN) and six dogs chronically administered the angiotensin-converting-enzyme inhibitor (ACEI) Benazepril. After 7 days of pacing, cardiac output was significantly higher and total peripheral resistance (TPR) lower in the ACEI compared with the AN dogs. Cumulative sodium and water balance increased significantly in both groups, but after 7 days of pacing there were no significant differences between groups. However, the rate of increase in sodium and water balance was significantly less in the ACEI group. Effective renal plasma flow decreased in the AN and ACEI groups during pacing, but there were no between-group differences, and no significant changes in glomerular filtration rate (GFR) occurred in either group. In the AN dogs, pacing was continued for 7-21 days until the onset of decompensated heart failure. Urinary sodium excretion increased on the first day of ACEI infusion during this stage but returned to pre-ACEI levels during the next 2-3 days. No significant improvement in cardiac output was measured during ACEI in decompensated heart failure. These data suggest that chronic ACEI administration can improve renal and cardiac function in early heart failure without impairing GFR but is less chronic ACEI administration can improve renal and cardiac function in early heart failure without impairing GFR but is less effective in later, decompensated stages.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Obesity-induced hypertension. Renal function and systemic hemodynamics.

This study examined the control of renal hemodynamics and tubular function, as well as systemic hemodynamics, during obesity-induced hypertension in chronically instrumented conscious dogs. Mean arterial pressure, cardiac output, and heart rate were monitored 24 hours a day using computerized methods, water and electrolyte balances were measured daily, and renal hemodynamics were measured each week during the control period and 5 weeks of a high-fat diet. After 7 to 10 days of control measurements, 0.5 to 0.9 kg of cooked beef fat was added to the regular diet, and sodium intake was maintained constant at 76 mmol/d throughout the study. After 5 weeks of the high-fat diet, body weight increased from 24.0 +/- 1.0 to 35.9 +/- 4.9 kg, mean arterial pressure increased from 83 +/- 5 to 100 +/- 4 mm Hg, cardiac output increased from 2.86 +/- 0.27 to 4.45 +/- 0.55 L/min, and heart rate rose from 68 +/- 5 to 107 +/- 9 beats per minute. Associated with the hypertension was an increase in cumulative sodium balance to 507 +/- 107 mmol after 35 days and a rise in sodium iothalamate space, an index of extracellular fluid volume, to 131 +/- 4% of control. Sodium retention was due to increased tubular reabsorption, because glomerular filtration rate and effective renal plasma flow increased throughout the 5 weeks of the high-fat diet, averaging 135 +/- 4% and 149 +/- 19% of control, respectively, during the fifth week of the high-fat diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Pressure natriuresis and angiotensin II in reduced kidney mass, salt-induced hypertension.

In normal subjects, high sodium intake causes little change in mean arterial pressure (MAP). However, MAP is sodium sensitive after reduction of kidney mass. The present study examined the role of increased renal artery pressure and decreased angiotensin II (ANG II) formation in maintaining sodium balance during high sodium intake in dogs with reduced kidney mass. In seven dogs with pressure natriuresis intact, increasing sodium intake from 36 to 466 meq/day for 7 days raised MAP from 91 +/- 2 to 106 +/- 2 mmHg. Sodium excretion increased promptly and cumulative sodium balance increased by only 80 +/- 26 meq after 7 days of high sodium intake. When renal perfusion pressure was servo-controlled to prevent pressure natriuresis, comparable increases in sodium intake raised MAP from 88 +/- 2 to 128 +/- 4 mmHg after 7 days. Sodium excretion rose to match intake, but cumulative sodium balance increased by 226 +/- 34 meq after 7 days. In dogs in which ANG II levels were held constant by converting enzyme inhibition and constant ANG II infusion (2 ng.kg-1.min-1 iv), raising sodium intake for 7 days elevated MAP from 126 +/- 2 to 146 +/- 4 mmHg after 7 days while increasing cumulative sodium balance by 212 +/- 29 meq. When renal perfusion pressure was servo-controlled and ANG II levels held constant, raising sodium intake elevated MAP from 125 +/- 3 to 166 +/- 11 mmHg and increased cumulative sodium balance by 399 +/- 128 meq. These data indicate that pressure natriuresis and decreased ANG II formation are important in minimizing sodium retention and hypertension during high sodium intake. However, other mechanisms can increase sodium excretion independent of pressure natriuresis and suppression of ANG II during salt-induced hypertension.

Angiotensin II↗

PubMed1992

Comparison of renal actions of urodilatin and atrial natriuretic peptide.

A 32-amino acid atrial natriuretic peptide (ANP)-like peptide, putatively synthesized by the kidney, has recently been isolated from human urine. This peptide, urodilatin (Uro), is structurally similar to the 28-amino acid ANP, suggesting that they might have similar actions on renal fluid and electrolyte excretion. The purpose of this study was to characterize the direct renal actions of low doses of Uro infusion and to compare them with the effects of equimolar intrarenal infusions of either ANP or the 24-amino acid atriopeptin III (AP III). Synthetic Uro was infused into the renal artery of pentobarbital sodium-anesthetized mongrel dogs (n = 8) at 0.14, 0.28, and 1.43 pmol.kg-1.min-1 while renal perfusion pressure was servo-controlled at 100 mmHg. Uro infusion at 1.43 pmol.kg-1.min-1 increased sodium excretion from an average control of 57.4 +/- 10.1 to 159.0 +/- 24.4 mueq/min. Uro infusion at the highest dose also increased potassium excretion (28.0 +/- 4.5 vs. 40.4 +/- 7.4 mueq/min), chloride excretion (56 +/- 11 vs. 155 +/- 22 mueq/min), and urine volume (0.54 +/- 0.12 vs. 1.22 +/- 0.25 ml/min). Fractional lithium excretion, a marker for proximal tubular sodium reabsorption, was not altered by Uro infusion, nor were urinary guanosine 3',5'-cyclic monophosphate excretion, glomerular filtration rate, or effective renal plasma flow changed. Equimolar infusions of these low doses of either alpha human ANP (n = 6) or AP III (n = 8) had no effect on any of the measured variables. Thus, within the range of doses used in this study, Uro was a more effective natriuretic and diuretic agent than either ANP or AP III.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Obesity-associated hypertension. Hyperinsulinemia and renal mechanisms.

Hyperinsulinemia and insulin resistance have been postulated to link obesity and hypertension. Evidence supporting this concept derives mainly from epidemiological studies showing a correlation between insulin resistance, hyperinsulinemia, and blood pressure and from short-term studies suggesting that insulin has renal and cardiovascular actions that, if sustained, could elevate blood pressure. However, a cause-and-effect relation between insulin and hypertension has not been clearly established. Recent studies indicate that chronic hyperinsulinemia, similar to that found in obese hypertensive patients, did not raise blood pressure in normal dogs, even when renal excretory capability was reduced by prior removal of kidney mass. Chronic insulin infusion also failed to elevate blood pressure in dogs maintained on a high sodium intake and did not potentiate the long-term blood pressure responses to angiotensin II or norepinephrine. The presence or absence of insulin resistance may not be a major factor in determining the blood pressure response to hyperinsulinemia since chronic insulin infusion also failed to cause hypertension in obese, insulin-resistant dogs. Although hyperinsulinemia causes transient sodium retention, sustained decreases in renal excretory capability sufficient to cause chronic hypertension did not occur in dogs. In rats, insulin infusion causes small increases in blood pressure, although several characteristics of the hypertension (e.g., salt-sensitivity) differ from those observed in obese human hypertensive patients. Whether humans more closely resemble dogs or rats with respect to their long-term cardiovascular responses to insulin remains to be determined. However, very high insulin levels in humans with insulinoma do not cause hypertension, and several studies suggest that there is only a weak correlation between plasma insulin concentration and blood pressure in normal humans. Therefore, additional factors besides hyperinsulinemia per se may be responsible for a major component of obesity-associated hypertension.

Animals↗

PubMed1992

Hypertension during chronic hyperinsulinemia in rats is not salt-sensitive.

The goal of this study was to examine the chronic blood pressure and renal actions of insulin in conscious rats and to determine whether the blood pressure response to insulin is salt-sensitive. The effects of chronic hyperinsulinemia were examined in three groups of Sprague-Dawley rats given low sodium (LS rats, 0.6 meq/day), normal sodium (NS rats, 3.0 meq/day), or high sodium (HS rats, 11.4 meq/day) intakes. After 5-7 days of acclimation and 4 days of control measurements, insulin was infused 24 hr/day (1.5 milliunit/kg/min i.v.) for 7 days, and euglycemia was maintained by infusion of glucose (22 mg/kg/min i.v.). Mean arterial pressure was recorded continuously 19 hr/day, using computerized techniques, from chronically implanted aortic catheters. Chronic insulin infusion increased arterial pressure similarly in the three groups of rats, from 91 +/- 2 to 104 +/- 4 mm Hg in LS rats (n = 6), from 86 +/- 2 to 104 +/- 4 mm Hg in NS rats (n = 5), and from 91 +/- 2 to 105 +/- 8 mm Hg in HS rats (n = 5). There were no significant changes in plasma renin activity or glucose concentration in any group during insulin infusion. Control sodium excretions were 0.5 +/- 0.1, 2.3 +/- 0.1, and 9.3 +/- 0.6 meq/day in LS, NS, and HS rats, respectively, and there were no significant changes in urinary sodium excretion or cumulative sodium balance during 7 days of insulin infusion in any of the groups. These observations indicate that chronic hyperinsulinemia in rats produced hypertension that was not salt-sensitive and not dependent on sodium retention or increased renin secretion. Moreover, insulin-induced hypertension was associated with a shift of renal pressure natriuresis, since sodium balance was maintained at elevated arterial pressures.

Animals↗

PubMed1992

Insulin resistance, hyperinsulinemia, and obesity-associated hypertension.

Recent work to elucidate the cause of obesity-associated hypertension has focused on insulin resistance and hyperinsulinemia. A significant amount of epidemiologic and correlational evidence suggests a link between these factors and obesity-associated hypertension, and acute insulin infusion studies have revealed renal, neural, and cardiovascular effects of this hormone that, if maintained chronically, could cause hypertension. However, correlations and acute effects may not reliably predict a chronic cause-and-effect relationship, and the fundamental question of whether chronic increases in plasma insulin concentration per se can produce a sustained increase in arterial pressure has not been completely resolved. Recent studies designed to address this question directly have found no evidence of a hypertensive effect of insulin in normal dogs, or in dogs with a 70% reduction in kidney mass and given a high sodium intake. Chronic hyperinsulinemia also did not potentiate the pressor effects of angiotensin II or norepinephrine. In fact, hyperinsulinemia caused significant reductions in total peripheral vascular resistance in dogs and a decrease in arterial pressure. Furthermore, induction of insulin resistance in dogs made obese by being fed a high-fat diet eliminated the decrease in peripheral vascular resistance during chronic insulin infusion but did not uncover a pressor effect of hyperinsulinemia. In contrast, insulin infusion for up to 7 days produced a sustained increase in arterial pressure in rats. Although the mechanism for this pressor response is unknown, these data indicate either that there are major species differences in the chronic blood pressure response to insulin or that specific, presently unknown, conditions must exist in order for insulin to raise blood pressure. Also, it is not clear whether humans respond more like rats or dogs with respect to blood pressure changes during chronic hyperinsulinemia. However, it is apparent that obesity hypertension is probably much too complex to be ascribed to insulin resistance and hyperinsulinemia alone.

Animals↗

PubMed1991

The hemodynamic response to chronic hyperinsulinemia in conscious dogs.

This study describes the hemodynamic effects of chronic hyperinsulinemia in seven normal dogs. Insulin infused at 1 mU/kg/min together with glucose at 14 mg/kg/min for 7 days increased fasting plasma insulin concentration approximately six-fold. Plasma glucose concentration was unchanged on day 1 but was below control on day 6. Mean arterial pressure decreased from 81 +/- 4 mm Hg to 70 +/- 3 mm Hg, while cardiac output increased to 30 +/- 8% above control by day 7. Total peripheral resistance decreased to 69 +/- 5% of control. Urinary sodium excretion was significantly decreased and was accompanied by a 22% increase in extracellular fluid volume with no change in blood volume. All parameters returned to control levels during the recovery period. These data suggest that, in addition to promoting renal sodium retention, insulin may lower blood pressure and increase cardiac output through a peripheral vasodilatory effect.

Animals↗

PubMed1991

Sustained hyperinsulinemia increases arterial pressure in conscious rats.

A large body of correlational evidence relating plasma insulin levels and arterial pressure in obese hypertensives suggests that hyperinsulinemia may play a causal role in the development of hypertension in these subjects. However, experimental evidence supporting the ability of increased plasma insulin per se to increase blood pressure is lacking. The goal of this study was to determine the effect of hyperinsulinemia on mean arterial pressure and renal electrolyte excretion in eight conscious rats. Arterial pressure was determined by sampling the signal from an abdominal aortic catheter once per minute, 19 h/day by computer. A 5-day intravenous insulin and glucose infusion that increased plasma insulin concentration 43% significantly increased mean arterial pressure from 93 +/- 1 mmHg to an average of 101 +/- 2 mmHg for the 5-day experimental period. Heart rate increased from 369 +/- 8 to 406 +/- 3 beats/min. Urinary sodium excretion transiently decreased on day 1 of insulin, but no significant sodium retention was measured after 5 days of insulin infusion, suggesting that the blood pressure increase was not volume mediated. There were no changes in any of these variables in eight vehicle-infused rats. These results suggest that hyperinsulinemia can increase mean arterial pressure in conscious rats, but the underlying mechanism remains to be elucidated.

Animals↗

PubMed1991

Chronic intrarenal hyperinsulinemia does not cause hypertension.

Hyperinsulinemia has been postulated to link obesity and hypertension via the antinatriuretic actions of insulin. The main goal of this study was to quantitate the importance of the direct intrarenal actions of insulin, independent of systemic effects, in altering blood pressure and renal function. This was accomplished by determining the responses to chronic intrarenal insulin infusion in uninephrectomized, chronically instrumented conscious dogs maintained on a 74 meq/day sodium intake. Insulin was infused at rates calculated to raise intrarenal, but not systemic, insulin to levels similar to those observed in obese hypertensive dogs. Intrarenal insulin infusion (0.6 mU.kg-1.min-1) for 7 days caused transient decreases in sodium excretion but no significant changes in potassium excretion. Mean arterial pressure did not change during 7 days of insulin infusion, averaging 93 +/- 4 mmHg during control and 93 +/- 3 mmHg during insulin infusion. Intrarenal insulin caused small increases in GFR but no significant changes in effective renal plasma flow or renal vascular resistance. These results demonstrate that insulin causes transient decreases in sodium excretion, but chronic intrarenal hyperinsulinemia does not elevate blood pressure in normal dogs. Additional factors other than the direct sodium-retaining effects of insulin may be important in raising blood pressure in obesity-associated hypertension.

Animals↗

PubMed1990

ANF and postprandial control of sodium excretion in dogs with compensated heart failure.

The changes in plasma immunoreactive atrial natriuretic factor (iANF) and urinary Na excretion that occur in response to an oral load of Na and to infusion of synthetic atrial natriuretic factor (ANF) were examined in conscious dogs with an arteriovenous (AV) fistula and chronic compensated high-output heart failure. After ingestion of a meal containing 125 meq Na, plasma iANF and right atrial pressure increased from high basal levels of 506 +/- 46 pg/ml and 96 +/- 5 mmH2O to peak responses of 728 +/- 43 pg/ml (P less than 0.05) and 104 +/- 6 mmH2O (P less than 0.05). These increases were associated with a brisk postprandial natriuresis and diuresis of a magnitude previously observed in normal dogs. Synthetic ANF infusions that achieved plasma iANF levels of similar and higher magnitude to those observed during the feeding experiments did not produce a significant natriuresis in these AV fistula dogs. In separate series of experiments, chronic effects of normal and low-Na diets on daily Na excretion and postabsorptive plasma iANF, renin, and aldosterone were studied in normal and AV fistula dogs. During the normal Na diet of 40 meq/day, both groups had normal levels of renin and aldosterone, but Na balance was achieved in AV fistula animals in the presence of a fourfold elevation in plasma iANF compared with normal dogs (P less than 0.05). During 2 wk of Na restriction, cumulative negative Na balance and marked stimulation of renin and aldosterone were similar in normal and AV fistula animals, but plasma iANF did not change significantly in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1990

Atrial natriuretic peptide induces sustained natriuresis in conscious dogs.

Although acute infusions of atrial natriuretic peptide (ANP) often cause natriuresis, these effects are not sustained, possibly because of reductions in arterial pressure or other compensatory adaptations. The aim of this study was to determine whether physiological increases in intrarenal ANP levels cause sustained natriuresis if changes in arterial pressure and other neurohumoral influences that might obscure the renal responses are controlled. Changes in renal function were quantitated during chronic unilateral renal arterial infusion of ANP at rates of 1, 2, and 4 ng.kg-1.min-1 in conscious dogs (n = 7) with the urinary bladder split to allow continuous measurement of renal excretion in the ANP-infused and contralateral, vehicle-infused kidneys. There was no change in mean arterial pressure at any infusion rate. During 1 ng.kg-1.min-1 infusion of ANP for 5 days, the renal excretory responses were small and variable. However, during 2 and 4 ng.kg-1.min-1 ANP infusion for 7 days, sodium excretion averaged 37.2 +/- 10.0 and 134.8 +/- 19.0% greater, respectively, in the ANP-infused kidneys compared with the vehicle-infused kidneys but there were no changes in glomerular filtration rate or effective renal plasma flow. These results demonstrate that when compensatory changes in arterial pressure and neurohumoral factors are controlled, ANP, at physiological concentrations, causes marked increases in renal excretion. This study supports the concept that ANP's effects to increase renal excretory capability could play a role in long-term control of arterial pressure and body fluid homeostasis.

Aldosterone↗

PubMed1990

Intrarenal atrial natriuretic peptide infusion lowers arterial pressure chronically.

Chronic intravenous infusions of atrial natriuretic peptide (ANP) have been shown to lower mean arterial pressure (MAP) in both normal and hypertensive animals. However, the importance of the renal actions of ANP in mediating this hypotension is unknown. This study was designed to determine whether physiological or pathophysiological increases in intrarenal ANP levels influence long-term control of arterial pressure. ANP was infused into the renal artery of seven conscious, uninephrectomized, chronically instrumented dogs at 1, 2, and 4 ng.kg-1.min-1 for 7 days at each dose, followed by a recovery period. Then ANP was infused intravenously following the same protocol. MAP decreased from 88 +/- 3 to 78 +/- 3 mmHg during intrarenal infusion of 1 ng.kg-1.min-1 ANP; increasing the ANP infusion rate did not result in a further reduction in MAP. Systemic arterial plasma ANP concentration did not change from control (15 +/- 5 pg/ml) during 1 or 2 ng.kg-1.min-1 intrarenal ANP infusion but increased slightly during 4 ng.kg-1.min-1 intrarenal ANP infusion, averaging 53 +/- 11 pg/ml. Renal arterial plasma ANP concentrations were calculated to increase to approximately 120 +/- 5, 248 +/- 11, and 484 +/- 22 pg/ml during 1, 2, and 4 ng.kg-1.min-1 intrarenal ANP infusion, respectively. Intravenous ANP infusion did not alter MAP at 1 ng.kg-1.min-1, but MAP was slightly lower than control during 2 and 4 ng.kg-1.min-1 ANP infusion and remained below control during the postinfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Atrial natriuretic factor and blood pressure control: role of sodium and aldosterone.

This study examined the long-term actions of atrial natriuretic factor (ANF), at physiological levels, on renal function and mean arterial pressure (MAP) and the importance of Na intake and the renin-angiotensin-aldosterone system in modulating those effects. After a control period, ANF was infused intravenously at a rate of 10 ng.kg-1.min-1 for 7 days, followed by 7 days of 20 ng.kg-1.min-1 and 7 days of recovery. After 7 days of ANF at 10 ng.kg-1.min-1, MAP decreased from 87 +/- 3 to 80 +/- 2 mmHg in normal dogs on low sodium intake (LS, 7 meq Na/day) and from 89 +/- 2 to 79 +/- 2 mmHg in adrenalectomized dogs (ADX, 7 meq Na/day) given constant mineralocorticoid replacement. In both groups, no significant change in glomerular filtration rate (GFR) was observed, although sodium excretion increased transiently. ANF failed to cause significant changes in MAP, GFR, or sodium excretion in normal dogs on high sodium intake (HS, 269 meq Na/day). In LS and HS no long-term effects of ANF on plasma renin activity (PRA) and aldosterone were observed. In ADX, as expected, no change in aldosterone was observed. Thus, in normal and adrenalectomized dogs on LS, chronic ANF infusion caused sustained reductions in MAP. HS markedly attenuated the hypotensive effect of ANF. Our data suggest that the long-term effect of ANF is salt sensitive but that decreases in PRA and aldosterone are not essential for the long-term hypotensive effect of ANF.

Adrenalectomy↗

PubMed1990

Chronic hyperinsulinemia and blood pressure. Interaction with catecholamines?

Although hyperinsulinemia and increased adrenergic activity have been postulated to be important factors in obesity-associated hypertension, a cause and effect relation between insulin, catecholamines, and hypertension has not been established. The aim of this study was to determine whether chronic hyperinsulinemia, comparable with that found in obese hypertensive patients, causes hypertension in normal dogs, increases plasma catecholamines, or potentiates the blood pressure effects of norepinephrine. In six normal dogs, insulin infusion (1.0 milliunits/kg/min) for 7 days, with euglycemia maintained, increased fasting insulin fourfold to sixfold. However, mean arterial pressure did not increase, averaging 99 +/- 2 mm Hg during the control period and 91 +/- 3 mm Hg during the 7 days of insulin infusion. Insulin did not alter plasma norepinephrine or epinephrine, which averaged 171 +/- 27 and 71 +/- 14 pg/ml, respectively, during the control period and 188 +/- 29 and 45 +/- 12 pg/ml during the 7 days of insulin infusion. In six dogs, norepinephrine was infused (0.2 microgram/kg/min) for 7 days to raise plasma norepinephrine to 2,940 +/- 103 pg/ml. Insulin infusion (1.0 milliunits/kg/min) for 7 days during simultaneous infusion of norepinephrine did not further increase mean arterial pressure, which averaged 101 +/- 3 during norepinephrine and 98 +/- 2 mm Hg during insulin plus norepinephrine infusion. Thus, chronic hyperinsulinemia did not increase mean arterial pressure or plasma catecholamines and did not potentiate the blood pressure actions of norepinephrine. These observations provide no evidence that chronic hyperinsulinemia or interactions between insulin and plasma catecholamines cause hypertension in normal dogs.

Animals↗

PubMed1990

Abnormal pressure natriuresis. A cause or a consequence of hypertension?

In all forms of chronic hypertension, the renal-pressure natriuresis mechanism is abnormal because sodium excretion is the same as in normotension despite the increased blood pressure. However, the importance of this resetting of pressure natriuresis as a cause of hypertension is controversial. Theoretically, a resetting of pressure natriuresis could necessitate increased blood pressure to maintain sodium balance or it could occur secondarily to hypertension. Recent studies indicate that, in several models of experimental hypertension (including angiotensin II, aldosterone, adrenocorticotrophic hormone, and norepinephrine hypertension), a primary shift of renal-pressure natriuresis necessitates increased arterial pressure to maintain sodium and water balance. In genetic animal models of hypertension, there also appears to be a resetting of pressure natriuresis before the development of hypertension. Likewise, essential hypertensive patients exhibit abnormal pressure natriuresis, although the precise cause of this defect is not clear. It is likely that multiple renal defects contribute to resetting of pressure natriuresis in essential hypertensive patients. With long-standing hypertension, pathological changes that occur secondary to hypertension must also be considered. By analyzing the characteristics of pressure natriuresis in hypertensive patients and by comparing these curves to those observed in various forms of experimental hypertension of known origin, it is possible to gain insight into the etiology of this disease.

Animals↗

PubMed1989

DOCA administration and atrial natriuretic factor in dogs with chronic heart failure.

The chronic reserve for the secretion of atrial natriuretic factor (ANF) was studied in conscious dogs with an arteriovenous (a-v) fistula, a model of high-output heart failure. After the first 7 days of marked sodium retention after creation of the a-v fistula, the animals regained sodium balance for the subsequent 3 wk. This compensatory natriuresis occurred in the presence of significant increases in right atrial pressure and was associated with marked and sustained elevations in plasma ANF and with the return of plasma renin and aldosterone to base-line values. The cardiac reserve for ANF secretion was further evaluated in these dogs with compensated high-output heart failure during additional progressive elevations in cardiac filling pressures induced by 3 wk of deoxycorticosterone acetate (DOCA) administration. During the DOCA regimen, plasma ANF increased an additional twofold from its high base line. Arterial blood pressure increased by 6-12 mmHg, and plasma renin activity was suppressed. However, the animals consistently retained sodium, and the high plasma levels of ANF were unable to counterbalance the sodium-retaining actions of DOCA. After termination of DOCA, the dogs exhibited a marked natriuresis, and all the hemodynamic and hormonal parameters returned to pre-DOCA control levels. This longitudinal study demonstrates that the cardiac reserve for chronic ANF secretion is well maintained in dogs with an a-v fistula during progressive cardiac volume overload. The present results suggest that the ANF endocrine system may represent one chronic compensatory mechanism to achieve sodium balance in heart failure when there is concomitant normalization of the renin-aldosterone system.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗