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Biomedical subjects

H D Kleinert

Publications and source records attributed to H D Kleinert.

At least 55 records · Page 3Linked to original sources
PubMed1986

Cardiovascular effects of atrial natriuretic factor in anesthetized and conscious dogs.

Atrial natriuretic factor lowers blood pressure in normotensive and hypertensive animal models. The present study examined the mechanism of the blood pressure-lowering effect in 10 normotensive dogs. Four awake dogs previously instrumented with electromagnetic flow probes for measurement of cardiac output and catheters for systemic hemodynamic and cardiac dynamic measurements were studied. After a 30-minute control period, a 3 micrograms/kg bolus followed by 0.3 micrograms/min/kg of a 24-residue synthetic atrial natriuretic factor was infused for 30 minutes, followed by a 1-hour recovery period. Mean arterial pressure fell significantly during infusion (control, 125 +/- 4; infusion, 108 +/- 5; recovery, 125 +/- 9 mm Hg; p less than 0.05) and was accompanied by a slight but significant bradycardia (control, 144 +/- 7; infusion, 134 +/- 5; recovery, 145 +/- 7 beats/min; p less than 0.05). Significant reductions in cardiac output (control, 2.66 +/- 0.60; infusion, 2.18 +/- 0.60; recovery, 2.74 +/- 0.60 L/min; p less than 0.05), stroke volume (control, 18.4 +/- 3.9; infusion, 16.0 +/- 4.2; recovery, 19.0 +/- 3.7 ml/beat; p less than 0.05), and maximum increase in rate of change of left ventricular systolic pressure (control, 2475 +/- 200; infusion, 2088 +/- 216; recovery, 2487 +/- 243 mm Hg/sec; p less than 0.05) were also observed during infusion. No significant changes in total peripheral resistance or central venous pressure were noted, although the latter tended to fall during infusion. A similar pattern was observed in six pentobarbital-anesthetized dogs, except that infusion of atrial natriuretic factor did not induce bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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

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

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↗
PubMed1983

Pheochromocytoma and prazosin.

Prazosin was used to control the signs and symptoms of excessive alpha-adrenergic activity in four patients with pheochromocytomas. Long-term dosage requirements were predicted by the blood pressure response to a single 1-mg oral dose. However, surgical management of the pheochromocytomas was inadequate with prazosin alone, and intravenous phentolamine was required to suppress the pressor surges generated by the tumor during surgical manipulation and excision.

Adult↗
PubMed1983

Microregional blood flow and high energy phosphates under conditions of high O2 supply in left ventricular subendocardium.

Blood flow and high energy phosphate (HEP) content were determined simultaneously in multiple microregions of the left ventricular subendocardium in 49 anaesthetized open-chest rabbits, to determine the relationship between the parameters during high O2 supply with hypercapnia and chromonar treatment. ATP and CP content were quantitated in quick-frozen hearts by fluorometry in 1-2 mg sites where perfusion was measured by H2 clearance employing bare-tipped platinum electrodes. Both hypercapnia and chromonar elevated subendocardial tissue perfusion approximately 30% and O2 supply 45% above control. Blood flow was normally distributed with either treatment, but was more homogeneous with hypercapnia. Neither treatment altered absolute levels of either HEP, but the variance of ATP was less than control. CP distribution was normal in both treatments. There was no significant linear correlation between blood flow and HEP under hypercapnia or chromonar treatment. We conclude that tissue HEP content is a variable not only dependent on O2 supply and blood flow, but also on the size of the ATP and CP pool and the energy demand of the local microregion. The variability of ATP in microregions of the rabbit subendocardium is reduced under conditions of high O2 supply.

Adenosine Triphosphate↗
PubMed1982

Blood pressure during normal daily activities, sleep, and exercise. Comparison of values in normal and hypertensive subjects.

Blood pressure (BP) readings were taken every 15 minutes using a noninvasive ambulatory BP recorder during 24 hours in 25 subjects with normal BP, 25 with borderline hypertension, and 25 with established essential hypertension. Readings were analyzed for four situations: (1) physician's office, (2) work, (3) at home, and (4) asleep. Treadmill exercise tests were also performed on a separate occasion with the Bruce protocol. The 24-hour recording in all three groups showed the highest BPs at work and the lowest during sleep. The situational BP changes were generally similar, but both hypertensive groups differed from normal subjects in that they showed consistently higher BPs in the physician's office than at home, whereas normal subjects showed a similar rise of systolic pressure to that of normal subjects. Pressures recorded in the physician's office gave good predictions of the average 24-hour pressure in normal and established hypertensive subjects, but not in the borderline group; in such patients, 24-hour monitoring may be of particular value in establishing the need for treatment.

Adult↗
PubMed1982

Situational variations of blood pressure in ambulatory hypertensive patients.

Blood pressure and heart rate were recorded at 15-min intervals for 24 hr in 60 untreated patients with uncomplicated mild essential hypertension using a new automatic noninvasive portable recorder. During the recording, the patients went about their normal daily routine, of which they kept a detailed record. The data were analyzed for five different recording situations: in the clinic, at work, at home, asleep, and average of the entire 24-hr period. Twenty-four hour readings were also compared with previously obtained casual readings. Clinic readings were correlated with the average 24-hr values, but for individual patients clinic pressures were relatively poor predictors of 24-hr pressures. Pressures recorded in the clinic were also greater than average 24-hr values. Similar degrees of correlation were found between clinic, home, work, and sleep pressures. Pressures recorded in the clinic were similar to pressures at work but higher than at home or asleep. In contrast, heart rate was similar in all conditions except during sleep, when it was lower. Previously measured casual pressures were also correlated with the clinic readings, with systolic values being similar, but diastolic values higher in the clinic during the 24-hr recording. For patients with clinic diastolic pressures in the range 90-104 mm Hg, 24-hr pressures varied from 75 to 100 mm Hg. We conclude that pressures measured casually in the clinic do not accurately reflect average 24-hr pressures and that ambulatory recording is helpful in the evaluation of mildly hypertensive patients.

Adult↗
PubMed1982

Ambulatory monitoring in the evaluation of blood pressure in patients with borderline hypertension and the role of the defense reflex.

The differences between blood pressure (BP) readings taken in the clinic and during normal daily activities were assessed in two studies using a noninvasive ambulatory BP monitor (Avionics). In the first study 30 untreated hypertensive patients (17 with borderline pressures, average diastolic less than or equal to 95, and 13 established hypertensives, diastolics above 95) and 5 normotensive subjects had 30 readings taken in the physician's office and 30 while at home. Conventional sphygmomanometer BPs were also recorded in the office. In the borderline group home BPs were significantly lower than clinic BPs, whereas this difference was less marked for the established and normotensive group. In the second study BP was measured every 15 minutes for 24 hours in 25 normal subjects, 25 borderline and 25 established hypertensives, and readings categorized according to four recording situations: physician's office, work, at home, and sleep. BPs in all groups were highest at work and lowest asleep, and directional changes were similar. Both hypertensive groups showed higher BPs in the physician's office than at home, while normal subjects showed no difference. BPs recorded in the physician's office were good predictors of 24 hour average BP in normal and established hypertensive subjects, but not in the borderline group: in such patients 24 hour monitoring may be of particular value in evaluating the need for treatment.

Adolescent↗
PubMed1981

Blood flow and high-energy phosphates in microregions of left ventricular subendocardium.

Blood flow and high-energy phosphate (HEP) content were determined simultaneously in multiple microregions of left ventricular subendocardium in 29 normal anesthetized open-chest rabbits by use of a new micromethod to determine whether a direct linear relationship existed between these parameters. Tissue samples weighed 1-2 mg. ATP and creatine phosphate (CP) content were quantitated in quick-frozen hearts by fluorometry at sites where tissue perfusion was measured by H2 clearance by use of bare-tipped platinum electrodes. A series of validation studies were conducted to ensure that 1) no significant damage to the tissue surrounding the electrode occurred during the period of experimentation and 2) no significant loss of biochemical constituents had occurred due to labile processes during freezing or storage of the tissue. Blood flow, ATP, and CP values averaged 79.1 +/- 24.1 (SD) ml.min-1.100 g-1, 4.9 +/- 1.3 mumol/g tissue, and 8.0 +/- 3.0 mumol/g tissue, respectively, and are similar to those reported in studies using larger tissue samples. Correlation between the heterogeneous distribution of tissue perfusion and HEP revealed no direct linear relationship between these parameters in the normal unstressed rabbit subendocardium.

Adenosine Triphosphate↗
PubMed1980

Effects of carbon monoxide or low oxygen gas mixture inhalation on regional oxygenation, blood flow, and small vessel blood content of the rabbit heart.

The effects of lowering arterial O2 content, approximately 30%, by inspiration of low O2 or CO gas mixtures on regional myocardial relative tissue PO2, perfusion and small vessel blood content were studied in anesthetized, thoracotomized New Zealand white rabbits. Relative tissue PO2 and perfusion were determined polarographically. 59FeCl3 was used to determine small vessel blood content. In control, relative tissue PO2, perfusion and small vessel blood content averaged 33.1 mm Hg, 64.9 ml/min/100 g and 4.3 ml/100 g respectively in the subepicardium (EPI) and 22.7, 53.6 and 4.2 in the subendocardium (ENDO) of the left ventricle. Both hypoxic conditions increased regional blood flow, but to a lesser extent in the ENDO. Relative ENDO tissue PO2 fell more markedly than EPI in both conditions. Small vessel blood content increased more with CO than low O2. Regional O2 consumption, calculated by Krogh analysis, increased under both conditions. The response to lowered O2 content is thus an increase in flow, metabolic rate and the number of open capillaries with a lowered driving pressure for O2. The effects of these types of hypoxia appear more severe in the ENDO.

Animals↗
PubMed1978

Alterations in brain and muscle oxygenation during hypovolemia and replacement with plasma substitutes in rats.

A study was conducted on the effects of mild hemorrhage-induced hypovolemia and subsequent replacement with lactated Ringer's dextran or hemoglobin solution in 52 pentobarbital-anesthesized rats. Blood loss of 1.25% of body weight had no significant effect on the blood flow or relative tissue PO2 of the white matter of the cerebral cortex. Blood flow and relative tissue PO2 of the biceps brachii muscle were lowered during hypovolemia. Volume replacement with any of the three plasma substitutes had no effect on blood flow or relative tissue PO2 of cortical white matter. They all caused partial restoration of blood flow and relative tissue PO2 in the biceps brachii muscle. Full return in the muscle was not achieved, nor were there any significant differences between the treatment groups.

Animals↗
PubMedDate not supplied

Purification, sequencing and synthesis of natriuretic and vasoactive rat atrial peptide.

Mammalian atria contain potent natriuretic and diuretic substances which exist in high- and low-molecular-weight forms and which appear to be associated with atrium-specific granules. The natriuretic effect of atrial extract is largely accountable for by its renal haemodynamic effects; atrial extracts also antagonize hormone- and non-hormone-induced contraction of the isolated rabbit aorta and isolated rat kidney vasculature. We have completely purified a low-molecular-weight natriuretic and vasoactive substance from rat atria and characterized it as a 24-amino acid peptide. Synthetic peptide, produced by solid-phase synthesis, mimics biological effects of crude atrial extract and purified peptide; its activity is enhanced by slow oxidation, suggesting a disulphide (Cys 4-Cys 20) configuration for the native peptide. If secreted into blood, this atrial natriuretic peptide (' auriculin B') could be a novel peptide hormone of considerable importance to renal and cardiovascular homeostasis.

Amino Acid Sequence↗