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Biomedical subjects

T E Lohmeier

Publications and source records attributed to T E Lohmeier.

54 records · Page 3Linked to original sources
PubMed1977

Mechanisms involved in two-kidney renal hypertension induced by constriction of one renal artery.

Changes in plasma renin activity (PRA) and sodium balance were studied in hypertensive rabbits and dogs with one renal artery constricted and the other kidney intact (two-kidney hypertension); aldosterone secretion was measured also in the chronic hypertensive rabbits. Both PRA and aldosterone secretion were normal in some chronic hypertensive rabbits but elevated in others. Sodium balance studies revealed that some severely hypertensive rabbits with elevated PRA were in spontaneous negative sodium balance. Unlike the rabbit, PRA was never increased in the chronic hypertensive dog and sodium balance was normal. Infusion of [Sar1, Ala8]angiotensin II (P-113) decreased arterial pressure and aldosterone secretion in those hypertensive rabbits with elevated PRA but not in those rabbits with normal PRA; P-113 also did not decrease arterial pressure in the chronic hypertensive dog unless sodium depletion was superimposed. In the conscious two-kidney dog, acute renal artery stenosis increased both arterial pressure and PRA within minutes, and P-113 blocked the rise in pressure associated with the increase in PRA. Therefore, although apparent species differences between the rabbit and the dog occur, the present data indicate that neither increased PRA nor excess salt retention is essential to the chronic maintenance of two-kidney hypertension in these two species; however, in the dog a role for angiotensin II in the acute phase is indicated.

Adrenal Cortex Hormones↗
PubMed1976

Renin-angiotensin-aldosterone system in experimental renal hypertension in the rabbit.

Hypertension was produced in 25 rabbits by constricting the right renal artery and leaving the opposite kidney intact (two-kidney hypertension). After 30 days mean arterial pressure and plasma renin activity (PRA) were significantly elevated (P less than 0.01), and arterial pressure was correlated with PRA (r = 0.551, P less than 0.01); however, not all hypertensive rabbits had elevated PRA, and in animals in which sodium balance was monitored, only rabbits in negative sodium balance had increased levels of PRA. To investigate the role of angiotensin II (A-II) in the hypertension, [1-sarcosine,8-alanine]angiotensin II was infused at 6 mug/kg per min for 30 min in anesthetized hypertensive animals (n = 25). For the group, arterial pressure fell significantly (P less than 0.01), but several animals with minimal hypertension failed to give a depressor response. The declines in arterial pressure were highly correlated with PRA (r = 0.853, P less than 0.01). Aldosterone secretion in hypertensive animals was correlated with PRA (r = 0.851, P less than 0.01). Thus, two-kidney hypertension in the rabbit persists with normal PRA, but during periods of spontaneous sodium depletion, A-II plays a role in the maintenance of the hypertension.

Adrenal Glands↗
PubMed1976

Evidence for an intrarenal beta receptor in control of renin release.

Infusion of isoproterenol intravenously in normal dogs at rates of 0.10 or 0.018 mug/min per kg body wt increased renin secretion; at the lower infusion rate arterial pressure (AP) and renal blood flow (RBF) were unchanged. Isoproterenol was also infused into the renal artery in normal dogs at 0.10 mug/min per kg; renin secretion increased in association with an increase in RBF but AP was unchanged. Plasma K concentration was consistently decreased in all three of the above experiments and because hypokalemia is known to increase renin release isoproterenol was not infused intrarenally at the lower rate; the decrease in plasma K level precluded relating the entire response in renin release to isoproterenol. Intrarenal infusion of propranolol at 0.05 mg/kg per h in Na-depleted dogs decreased renin secretion whereas intravenous infusion at the same dose failed to alter renin release. Intrarenal infusion of propranolol at this rate in Na-depleted dogs with a denervated, nonfiltering kidney also decreased renin release. In contrast, intrarenal infusion of phentolamine or phenoxybenzamine in normal dogs failed to alter renin secretion in doses that blocked alpha-adrenergic receptors. These experiments provide strong evidence for an intrarenal beta-adrenergic receptor that mediates renin release, and it seems likely from the experiment in the denervated, nonfiltering kidney that the receptor is located in the juxtaglomerular cells.

Animals↗
PubMed1976

Mineralocorticoid activity of 18-OH-DOC and DOCA in dogs with an aortic-caval fistula.

The mineralocorticoid activity of 18-hydroxydeoxycorticosterone (18-OH-DOC) was measured during chronic electrolyte balance studies or during the postprandial increase in electrolyte excretion in conscious dogs with an aortic-caval fistula. In the chronic balance study, daily doses of DOCA and 18-OH-DOC ranging from 1 to 25 mg were administered intramuscularly for 3 consecutive days each, 6 h prior to feeding. For the postprandial study, 2-10 mg of DOCA and 18-OH-DOC were administered at feeding and postprandial electrolyte excretion was measured hourly for 6 h. Sodium and fluid retention in the dogs with an aortic-caval fistula was related to the dose of mineralocorticoid administered and equivalent sodium-retaining responses were achieved with 6-10 times more 18-OH-DOC than DOCA. Rapid absorption of both steroids was suggested from the postprandial measurements of urinary sodium excretion. Slight potassium retention occurred during the chronic administration of large doses of DOCA but the postprandial potassium responses produced by the steroids were variable and suggested a slight kaliuresis. The data also emphasize the importance of mineralocorticoids in sodium retention and ascites formation in this experimental model of high-output heart failure.

18-Hydroxycorticosterone↗
PubMed1976

Incidence and pathophysiological changes in chronic two-kidney hypertension in the dog.

Unilateral renal artery plication in dogs reduced renal blood flow by 80% and produced a sustained elevation in arterial pressure whereas plasma renin activity increased for only 4 days. Sodium was retained for 3 days after plication, but this response is similar to that after a sham operation. Of seven dogs studied chronically, elevated arterial pressure was sustained for 27 days or longer in six animals. In three dogs hypertension continued for 2 mo before collateral vessels developed and arterial pressure fell; ligation of these collaterals restored hypertension. Arterial pressure was unaffected by an infusion of [1-sarcosine, 8-alanine] angiotensin II in chronic hypertensive dogs on a normal sodium intake. This angiotensin antagonist lowered arterial pressure after sodium depletion, but became ineffective following rapid sodium repletion. Chronic hypertensive dogs showed normal responses to deoxycorticosterone acetate. These findings suggest that the renin-angiotensin system is not critically involved in maintenace of chronic two-kidney renovascular hypertension in the dog. The data also show that the homeostatic role played by the renin-angiotensin system in the maintenance of arterial pressure remained intact in chronic hypertension.

Angiotensin II↗
PubMed1976

Evidence that des-Asp1 angiotensin II mediates the renin-angiotensin response.

Studies were undertaken to compare and evaluate the influence of angiotensin II and its heptapeptide fragments, des-Asp-1-angiotensin II, at various receptor sites for angiotensin in both dogs and rats. Receptor sites evaluated were those which are found in the glomerulosa, reticularis, and fasiculata of the adrenal cortex, in the renal arterioles and the juxtaglomerular cells of the kidney, and in the peripheral arterioles. Both peptides produced similar changes in the steriod secretion profiles for aldosterones, corticosterone, and cortisol in the dog. In the rat, both peptides similarly increased aldosterone and corticosterone secretion; however, a larger dose of the competitive antagonist Sar-1,Ala-8-angiotensin II was required to block the steroid response to the heptapeptide. This finding suggests that receptor affinity for des-Asp-1-angiotensin II may be greater than its affinity for angiotensin II. Both peptides also decreased renin secretion and renal blood flow similarly in the dog. The pressor response to the heptapeptide was only about one-half the pressor response to angiotensin II in both the rat and dog studies. Collectively, these observations in dogs and rats suggest that des-Asp-1-angiotensin II may mediate the response to the renin-angiotensin system at both adrenal and renal receptors.

Adrenal Cortex↗
PubMed1976

Intrarenal site of action of calcium on renin secretion in dogs.

We studied the effects of intrarenal calcium infusion on renin secretion in sodium-depleted dogs in an attempt to elucidate the major site of calcium-induced inhibition of renin release. Both calcium chloride and calcium gluconate reduced renal blood flow and renin secretion while renal perfusion pressure was unchanged. These data indicate that calcium inhibition of renin secretion did not occur primarily at the renal vascular receptor; decreased renal blood flow is usually associated with increased renin secretion. Calcium chloride infusion increased urinary chloride excretion without affecting sodium excretion, and calcium gluconate failed to increase either sodium or chloride excretion. Also, the filtered loads of sodium and chloride were unchanged during the calcium infusions. These results give no indication that calcium inhibited renin secretion by increasing the sodium or chloride load at the macula densa. The effects of intrarenal calcium infusion on renin release were also assessed in dogs with a nonfiltering kidney in which renal tubular mechanisms could not influence renin secretion. The observation that calcium still suppressed renin release in these dogs provides additional evidence that the the major effect of calcium involved nontubular mechanisms. Thus, it appears likely that calcium acted directly on the juxtaglomerular cells to inhibit renin secretion.

Animals↗
PubMed1975

High-output heart failure in the dog: systemic and intrarenal role of angiotensin II.

Dogs with experimental high-output heart failure (HOF) exhibit marked retention of salt and water secondary to hypersecretion of both renin and aldosterone. The present study was undertaken to evaluate the systemic and intrarenal arteriolar action of angiotensin II (AII) in dogs with HOF and to provide additional information about the role of AII in low-output states. The intravenous infusion of a specific AII antagonist, [Sar1, Ala8]AII (6 mug/kg min-1), into conscious dogs with HOF decreased the mean arterial pressure (AP) from 101 +/- 7 to 83 +/- 7 mmHg (P less than 0.01) after 45 min of infusion. Intrarenal arterial infusion of the AII antagonist (0.2 and 2.0 mug/kg min-1) into anesthetized dogs with HOF also decreased AP and produced a marked increase in renal blood flow (RBF) with no changes in either creatinine clearance or sodium excretion. Similar results were obtained during the intrarenal infusion of the antagonist into sodium-depleted dogs and dogs with thoracic vena caval constriction, but not in normal dogs. The data demonstrate an important role for AII in the regulation of AP and RBF in high- and low-output states.

Angiotensin II↗
PubMed1975

Des-1-Asp-angiotensin II. Possible intrarenal role in homeostasis in the dog.

The relative effects of des-a-Asp-angiotensin 3I and angiotensin II on renal function, including renin secretion, were investigated in normal and sodium-depleted dogs. Intrarenal arterial infusion of the heptapeptide fragment into normal dogs at a rate which was calculated to increase blood levels by only 7 ng/100 ml decreased renal blood flow from 254 +/- 9 ml/min to 220 +/- 12 and 219 +/- 12 ml/min (P less than 0.01 for both values) after 10 and 30 minutes of infusion, respectively; renin secretion decreased from 502 +/- 214 ng/min to 253 +/- 109 and 180 +/- 53 ng/min (P less than 0.05 for both values). Infusion of angiotensin II at the same rate decreased renal blood flow from 251 +/- 26 ml/min to 224 +/- 22 and 220 +/- 16 ml/min (P less than 0.01 and 0.025, respectively) and decreased renin secretion from 374 +/- 25 ng/min to 166 +/- 76 and 131 +/- 37 ng/min (P less than 0.025 for both values). Neither peptide significantly changed mean arterial blood pressure, creatinine clearance, or excreted sodium in these dogs. Infusion of des-1-Asp-angiotensin II into sodium-depleted dogs decreased renin secretion from 1094 +/- 211 ng/min to 768 +/- 132 and 499 +/- 31 ng/min (P less than 0.025 for both values) after 10 and 30 minutes of infusion. Angiotensin II infusion decreased renin secretion from 1102 +/- 134 to 495 +/- 235 and 502 +/- 129 ng/min in these dogs (P less than 0.05 and 0.025, respectively). Neither peptide significantly altered renal blood flow, arterial blood pressure, creatinine clearance, or excreted sodium in the sodium-depleted dogs. The data demonstrated that these two peptides have similar effects on the renin secretory mechanism and the vascular receptor at the level of the renal arterioles.

Angiotensin II↗
PubMed1975

DES-ASP1--angiotensin II: possible role in mediating responses of the renin-angiotensin system.

In dexamethasone-treated dogs, both antiogensin II and its heptapeptide fragment (des-asp1-angiotensin II) stimulated the secretion of the adrenal steroids aldosterone, corticosterone, and cortisol. Further, there was no statistically significant difference in the steroidogenic potency of the two peptides. An interesting incidental finding was the decrease in PRA with both peptides, again with no demonstrable difference in the magnitude of the responses. The present data are consistent with the hypothesis that the heptapeptide mediates responses produced by the renin-angiotensin system in both the adrenals and the kidneys.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Changes in renal vascular sensitivity and arterial pressure associated with sodium intake during long-term intrarenal norepinephrine infusion in dogs.

Experiments were performed on conscious uninephrectomized dogs to determine the comparative effects of chronic intrarenal and intravenous norephrine (NE) infusion (0.27 microgram/kg/min) on the steady-state values for arterial pressure, plasma renin activity (PRA), and renal function at four levels of sodium intake (5, 40, 120 and 240 mEq/day). Arterial pressure was monitored continuously 24 hr/day with on-line computer techniques. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and plasma renin activity (PRA) were determined after sodium and water balance was achieved. During intrarenal NE infusion, ERPF and GFR decreased progressively from 15% to 30% and from 24% to 46% respectively, while renal vascular resistance increased progressively from 40% to 140% as sodium intake was increased from 10 to 240 mEq/day. Both ERPF and renal resistance, but not GFR, returned to control levels during intravenous NE infusion at each level of sodium intake and after terminating NE infusion. During intrarenal NE infusion the steady-state value for mean arterial pressure increased from a control of 105 to 118 mm Hg when the sodium intake was 10 mEq/day. Pressure then increased progressively from 118 to 135 mm Hg as the sodium intake was elevated from 10 to 240 mEq/day. Increases in arterial pressure associated with intravenous NE infusion were significantly smaller at each sodium level than those achieved with intrarenal NE infusion. At each level of sodium intake, PRA was elevated during intrarenal NE infusion and returned to control after NE infusion. Intravenous NE infusion did not increase PRA above control levels. The data are compatible with the concept that enhanced renal adrenergic activity could initiate and sustain hypertension chronically by basic alterations in renal function.

Animals↗
PubMedDate not supplied

Is vasopressin an important hypertensive hormone?

To generate quantitative data relating to the potential hypertensive activity of arginine vasopressin (AVP), 140 and 560 microunits AVP/kg/min were infused chronically in both normotensive dogs and dogs made hypertensive by chronic infusion of either angiotensin II (AII) or aldosterone. The lower rate of AVP infusion increased plasma AVP concentration from 0.4 +/- 0.1 microunits/ml. Mean arterial pressure (MAP) was recorded 24 hours per day, and all dogs were infused continuously with 800 ml of isotonic saline per day. During the initial days of AVP infusion in normotensive dogs, natriuresis, kaliuresis, and water retention were prominent and MAP increased progressively to a peak on Day 6 (30 mm Hg above control). Subsequently, diuresis ensued, net water retention decreased, and MAP fell progressively to only 13 mm Hg above control by Day 12 of AVP infusion. In contrast, in AII or aldosterone hypertensive dogs during AVP infusion, the natriuresis was greatly attenuated, water balance was unchanged or even negative, and MAP either did not increase or increased only transiently. When AVP infusion was terminated in dogs given only AVP, diuresis occurred, and MAP fell gradually over a period of hours to hypertensive levels. In marked contrast, cessation of AVP infusion in dogs with either AII or aldosterone hypertension was associated with a precipitous fall in MAP of 35 to 40 mm Hg within 1 hour: however, this reduction was only transient - over the subsequent hours, both salt and water retention occurred, and MAP returned to previous hypertensive levels. Thus, in the hypertensive models studied, high plasma levels of AVP had relatively weak hypertensive effects. Although variations in plasma AVP concentration were associated with rather pronounced acute effects on MAP, the long-term changes in MAP produced by AVP were either minimal or, in the case of the animals made hypertensive by other agents, nonexistent.

Aldosterone↗
PubMedDate not supplied

Malignant hypertensive crisis induced by chronic intrarenal norepinephrine infusion.

The purpose of the present study was to develop a controllable experimental model in the dog that would consistently and predictably produce a malignant hypertensive crisis, and to determine the sequential changes in renal function, salt and water balance, and hormones that are involved in the transition from benign to accelerated hypertension. Norepinephrine (NE) was infused continuously into the renal artery of unilaterally nephrectomized dogs that were maintained on 50 mEq sodium/day. The infusion rate of NE was increased each day according to the following schedule: 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 microgram/kg/min. During the first 4 to 5 days of intrarenal NE infusion, there was a progressive decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), and increases in plasma renin activity (PRA), mean arterial pressure (MAP), and filtration fraction. At the end of this period of benign hypertension, MAP had risen from a control value of 91 +/- 4 to 132 +/- 8 mm Hg, in association with approximately a 10-fold increase in PRA and a 40% reduction in renal function. Then, suddenly, during the subsequent 24-hour infusion period, the MAP increased abruptly in all animals (MAP = 156 +/- 8 mm Hg), and a hypertensive crisis occurred. This crisis was associated with the following: salt and water depletion, hyponatremia, hypovolemia and hemoconcentration, polydipsia, marked activation of the renin-angiotensin-aldosterone system, increased plasma cortisol concentration, hemolysis, marked impairment in renal function, lethargy, and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMedDate not supplied

Chronic angiotensin II infusion decreases renal norepinephrine overflow in conscious dogs.

Sympathetic nerve activity and in particular renal sympathetic nerve activity were monitored in six conscious dogs subjected to 6 days of intravenous angiotensin (ANG II) infusion (20 ng/kg/min). This was accomplished by measurement of both arterial and renal venous plasma catecholamine concentration. During the initial 4 hours of ANG II infusion, mean arterial pressure (MAP) increased 35 +/- 8 mm Hg from a control value of 101 +/- 4 mm Hg. Although there were no significant changes in arterial plasma norepinephrine (NE) concentration at this time (control = 148 +/- 40 pg/ml), arterial plasma epinephrine (E) concentration increased threefold (control 42 +/- 15 pg/ml). After 24 hours of ANG II infusion, MAP remained elevated (132 +/- 5 mm Hg), but plasma E concentration returned to control levels. From Days 2 through 6 of ANG II infusion, MAP was elevated approximately 40 mm Hg, but there were no chronic increases in either arterial plasma E or NE concentrations. In contrast to arterial plasma catecholamine concentration, renal vein plasma NE concentration (control = 216 +/- 27 pg/ml) actually decreased during both the acute (122 +/- 12 pg/ml) and chronic (103 +/- 26 pg/ml) phases of ANG II infusion. Moreover, renal NE overflow (renal venous plasma NE concentration-arterial plasma NE concentration X effective renal plasma flow), an index of renal sympathetic nerve activity, was depressed during the chronic phase of ANG II hypertension. These results, therefore, do not support the contention that the sympathetic nervous system mediates the hypertension produced by elevated plasma levels of ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMedDate not supplied

Chronic potentiation of vasoconstrictor hypertension by adrenocorticotropic hormone.

The chronic effects of ACTH on mean arterial pressure (MAP) and related variables were studied in dogs with both chronic norepinephrine (NE)- and chronic aldosterone-induced hypertension. MAP was recorded continuously for 24 hours/day, and sodium intake was 71 mEq/day. ACTH was infused for 8 days at a rate that does not increase MAP in normotensive dogs and yet a rate that produces pronounced mineralocorticoid and glucocorticoid effects. Chronic ACTH infusion in dogs with NE hypertension caused natriuresis, kaliuresis, diuresis, hypernatremia, hypokalemia, and suppression of PRA; additionally, there was either no net change in water balance or net water balance was positive. However, in marked contrast to dogs without pre-existing hypertension, in dogs with NE hypertension ACTH produced a pronounced additional increase in MAP of 39 to 63 mm Hg. Although ACTH markedly potentiated NE hypertension, high infusion rates of aldosterone (+6 mm Hg) and cortisol (-7 mm Hg) had relatively weak effects on MAP; further, in dogs with NE hypertension, the increase in MAP associated with simultaneous infusions of high rates of cortisol and aldosterone was equal to only approximately half of that produced by ACTH. In dogs with aldosterone hypertension, the changes in salt and water balance produced by ACTH were comparable to those that occurred when ACTH was administered to dogs with NE hypertension. In dogs with aldosterone hypertension, however, ACTH did not produce kaliuresis, hypernatremia, or hypokalemia; moreover, ACTH did not exacerbate aldosterone hypertension. Thus, the data indicate that the hypertensive effects of ACTH are manifested in conditions of reduced renal excretory capacity such as exist when plasma levels of the potent sodium -retaining hormone NE are inappropriately elevated. Finally, the hypertensive effects of ACTH cannot be accounted for simply on the basis of enhanced mineralocorticoid and glucocorticoid activity.

Adrenocorticotropic Hormone↗