Pulmonary atheroembolism via an AV shunt.

Although cholesterol crystal embolism can present with diffuse visceral involvement, lung lesions do not occur unless there is left to right circulatory shunting. Pulmonary atheroembolism was confirmed by histology in an elderly male with recent end-stage renal failure (ESRF) due to atheroembolic renal disease, who presented with massive hemoptysis and intractable respiratory failure. At autopsy, atheromatous degeneration of the aorta was observed and acute cholesterol emboli found in the kidneys, spleen, liver, stomach and lung. Cholesterol clefts were seen in pulmonary arterioles, and ischemic alveolar damage was present. The pulmonary arteries had no atheromatous changes. Intrapulmonary, intracardiac, and aortocaval shunting were not present. Pulmonary atheroembolism arising from a dialysis fistula has not been previously reported.

Cerebrospinal fluid kallikrein in spontaneously hypertensive and desoxycorticosterone acetate-salt hypertensive rats.

OBJECTIVE: To determine whether immunoreactive tissue kallikrein levels in cerebrospinal fluid (CSF) of spontaneously hypertensive rats (SHR) and desoxycorticosterone acetate (DOCA)--salt-treated hypertensive rats are elevated compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats. DESIGN: The present study was designed to test the hypothesis that the activity of the brain tissue kallikrein-kinin system is enhanced in hypertensive states. METHODS: Age-matched 18- to 19-week-old SHR and WKY rats, and Sprague-Dawley rats treated for 6 weeks either with 2 mg/kg per day DOCA subcutaneously and 0.9% saline in the drinking water, or with vehicle and tap water to drink, were studied. CSF was collected from a cannula inserted into the cisterna magna, and was frozen until the tissue kallikrein in the samples was measured by radioimmunoassay. Arterial pressure in the SHR and WKY rats was measured directly via a cannula inserted in the femoral artery or by tail-cuff plethysmography. RESULTS: In adult 18- to 19-week-old SHR the CSF kallikrein concentration was higher than in WKY rats. The CSF flow rate in SHR was also higher than in WKY rats. The rate of appearance of kallikrein in the CSF of SHR was twice that in WKY rats. Moreover, CSF kininogenase activity in SHR was significantly higher than that in age-matched WKY rats. In DOCA--salt hypertensive rats the CSF kallikrein concentration was higher than in vehicle-treated control rats. Acute elevation of blood pressure with a 120-min intravenous phenylephrine infusion did not change the CSF kallikrein concentration in 50 rats compared with vehicle-treated control rats. This is the first study to quantitate immunoreactive tissue kallikrein in the CSF of rats and to show elevated levels of CSF kallikrein in hypertensive rats compared with normotensive rats. CONCLUSION: The present data suggest that higher brain kallikrein activity in hypertensive rats may play a role in the development of elevated blood pressure.

[Renal sodium handling and renal dopaminergic activity in overweight normotensive subjects].

Recently, we reported that the blunted natriuretic ability related to an attenuation of renal dopaminergic activity might play an important role in the hypertensive mechanisms of overweight patients with essential hypertension. On the other hand, the interrelationships between obesity, blood pressure and renal sodium handling in normotensives (NT) have not been clear. The purpose of the present study is to reveal the role of renal dopaminergic activity on renal sodium handling in overweight NT. The study consisted of 52 hospitalized NT receiving a regular diet containing 200mEq of sodium, 75mEq of potassium, 2400kcal/day, who were divided into two groups of 31 non-obese (NNT) and 21 obese (ONT) subjects. NNT was categorized as the body mass index (BMI) less than, and ONT as the BMI equal to or more than, 25kg/m2. In the early morning, after overnight fasting, all subjects remained in a supine state and were examined for renal clearance. During the clearance period, mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance (Ccr), urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa) and of inorganic phosphorus (FEP) and urinary excretion of free dopamine (uDA) were determined. There were no significant differences in age, HR, Ccr or UNaV between the two groups. Higher MAP and lower FENa) were observed in ONT than in NNT, but the differences in these parameters were not statistically significant. However, FENa in ONT was significantly lower than in MAP-and Ccr-matched NNT. In addition, FENa correlated negatively with BMI in ONT, unlike in NNT. MAP was correlated positively with FENa, and a similar tendency was found between MAP and FEP in NNT, but not in ONT. On the other hand, there was no significant correlation between BMI and uDA in either NNT or ONT. This result was different from our previous data in patients with essential hypertension (EHT) in which BMI correlated with uDA positively in non-obese EHT and negatively in obese EHT. These findings suggest that blunted natriuretic ability may exist in ONT, and the role of renal dopaminergic activity related to the attenuated natriuretic ability in ONT may be less important than in obese EHT.

[A case of undiagnosed pheochromocytoma caused by negative metoclopramide test].

Metoclopramide (MCP), a dopamine antagonist, was recently used as the pharmacological test for the diagnosis of pheochromocytoma. There have been no reports involving false negative cases in the MCP test. We experienced a rare case of pheochromocytoma which showed a negative MCP test, and it caused a failure of the diagnosis. A 51-year-old man visited our hospital with a sudden onset of headache and palpitation. Blood pressure was 218/98 mmHg at another hospital. When he came to our hospital, blood pressure returned to normal (120/80 mmHg), and both serum adrenaline (E) and noradrenaline (NE) were within normal limits. A computed tomography, magnetic resonance imaging, and angiography demonstrated a 1.8 x 1.8 cm right adrenal mass. No changes in blood pressure and plasma catecholamine were observed following the injection of 10 mg of MCP. The pathologically resected right adrenal gland contained a typical pheochromocytoma which was 1.0 x 1.0 cm in size and weighed 8 g. The detailed mechanism of the negative MCP test in this case was not known but might be related to the small size of the tumor.

[Correlations between the coefficient of variation of RR intervals and sympathetic nerve activity following superior tilting in normotensive subjects and in patients with essential hypertension].

The relationship between changes in sympathetic nerve activity and those in parasympathetic tone with a change in position was investigated in patients with essential hypertension using the coefficient of variation of RR intervals on electrocardiograms (CVRR). Mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline concentration (pNA) and CVRR were measured in a supine position at rest and 20 min after having the head tilted 60 degrees superiorly in 10 normotensives (NT: 51.9 +/- 3.0 yrs) and 7 essential hypertensive patients (EHT: 51.0 +/- 2.8 yrs). After changing the position, CVRR decreased significantly in the NT, but not in the EHT; whereas, significant increases of both HR and pNA without significant changes in MAP were shown in both groups. A significant negative correlation between percentage changes in CVRR (% delta CVRR) and pNA (% delta pNA) were observed in the NT, but not in the EHT. However, there was no relationship of % delta CVRR to % delta MAP or to % delta HR in either group. It was suggested from the changes in CVRR that suppression of the parasympathetic tone, which occurs in the NT group corresponding to sympathetic augmentation to present a decrease in blood pressure with a change in position, may be impaired in the EHT group.

[Shy-Drager syndrome: its autonomic function, alpha 2 receptor density and mechanism of postprandial hypotension].

The autonomic function, platelet alpha 2 receptor (alpha 2R) density, and mechanism of postprandial hypotension were examined in a 58-year-old man with Shy-Drager syndrome (SDS). His chief complaints were orthostatic syncope and impotence. His blood pressure was kept within normal limits in a supine position, but severe hypotension and fainting occurred when he assumed an upright posture. There were diminished sweating response to warm stress, abnormal pupil reactions to drugs, lack of blood pressure elevation at phase IV during the Valsalva maneuver, and a lack of pressor response to hyperventilation and cold stress. The plasma norepinephrine levels (pNE) were very low in a supine position at rest and in a head-up tilt position. Severe blood pressure fall (hypotension) associated with a lack of pNE elevation occurred during an oral glucose tolerance test (oGTT). Platelet alpha 2R density increased and the pressor response to infused norepinephrine (NE-R) was pronounced. The heart rate response to injected atropine was clearly attenuated. The coefficient of the R-R interval variation in the ECG (CVRR), which may reflect parasympathetic activity, was markedly low at rest. In addition, a decrease in a head-up tilt position and increase during oGTT also resolved. These results indicate that a dysfunction of the parasympathetic and sympathetic nervous systems and the up-regulation in the alpha 2R system that leads to an increase in alpha 2R density in SDS are involved in this disease and that the mechanism of postprandial hypotension in SDS may be different from that in normal elderly subjects.

[Elevation of intracranial pressure during hemodialysis--continuous measurement of cerebrospinal fluid pressure in a patient with acoustic neurinoma].

Intracranial pressure (ICP) was continuously monitored in a thirty-two-year-old female of acoustic neurinoma complicated with chronic renal failure. Severe headache with vomiting has begun to appear during hemodialysis for several months, prompting a diagnosis of an obstructive hydrocephalus. Continuous ventricular drainage was placed after admission and changes of ICP were monitored during hemodialysis. Dynamic changes of electrolytes, protein, sugar, urea nitrogen, and creatinine levels in the cerebrospinal fluid (CSF) as well as osmolarity were measured every one hour during the hemodialysis. An increment of ICP started to occur gradually after initiation of hemodialysis reaching the maximum value 23 minutes later. It was spontaneously decreased to the initial level 8 minutes later followed by fluctuations thereafter consisting of the changes of 20 to 30 mmHg. A remarkable rise in osmotic pressure in CSF has been observed corresponding to the rise of ICP which created a large difference from the blood osmotic pressure that consistently decreased following the onset of hemodialysis. Whereas, the absolute values of all measured factors including electrolytes and urea nitrogen in CSF have decreased consistently which did not seem to contribute intermittent increment of osmotic pressure of CSF. The cause of ICP increment in our case was considered mainly due to increase of water content in the brain tissue caused by the widening of osmotic gradient between the CSF and blood, although the substances responsible to the actual increase of CSF osmotic pressure remained unclear.

A case of swallow syncope induced by vagovagal reflex.

A 65-year-old man experienced syncope associated with advanced atrioventricular (AV) block upon swallowing. Continuous electrocardiogram (ECG) monitoring revealed first and second degree AV block. ECG revealed advanced AV block (Max R-R 6.38 s) upon swallowing, a cold drink. Demand ventricular pacing alleviated his symptoms. In this patient, the advanced AV block might have been precipitated by a vagovagal reflex triggered by expansion of the esophagus, resulting in selective suppression of the atrioventricular node.

The role of Na,K-ATPase inhibitor on pressor responsiveness in patients with benign essential hypertension.

To clarify the role of Na,K-ATPase inhibitor in the enhanced pressor response to infused noradrenaline (NA-R) in patients with benign essential hypertension (EHT), NA-R, plasma noradrenaline concentration (PNA), and blood ionized calcium (Ca2+) were investigated before and after intravenous injection of ouabain in 15 normotensive subjects (NT) and 13 EHT. NA-R was enhanced by ouabain in both NT and EHT. The augmentation of NA-R following ouabain injection (delta NA-R) and % delta NA-R were significantly lower in EHT than in NT. Following ouabain injection, no significant change in PNA and blood Ca2+ was observed in both NT and EHT. NA-R negatively correlated with PNA and blood Ca2+, which were estimated just prior to noradrenaline infusion, before ouabain injection as well as after. After ouabain, the regression line between NA-R and PNA or blood Ca2+ shifted toward higher NA-R level in NT, unlike in EHT. These results suggest that an exogenous Na,K-ATPase inhibitor brings about a blunted enhancement of NA-R in EHT consistent with the presence of an endogenous Na,K-ATPase inhibitor in EHT.

Attenuated renal production of dopamine in patients with low renin essential hypertension.

Our previous studies have shown that a suppressed pressure natriuresis may contribute to the hypertensive mechanism in patients with essential hypertension (EHT), particularly in low renin patients (LRH). In this study, in order to clarify the role of renal dopaminergic activity in the blunted natriuresis of LRH, the conversion of 1-dopa (DOPA) to dopamine (DA) in the kidneys was investigated in 9 normotensive subjects (NT) and 20 EHT, including 15 normal renin EHT (NRH) and 5 LRH. All subjects were hospitalized and received a constant diet (Na:120mEq, K:75mEq daily). Plasma DOPA concentration (p-DOPA:HPLC-ECD), creatinine clearance (Ccr), urinary excretion of sodium (UNaV) and DA (UDA), as well as fractional excretion of sodium (FENa) were measured before and after the single oral administration of 1-DOPA (400mg). DOPA administration caused a significant increase of p-DOPA, UDA and FENa with undetectable DOPA levels in the urine in EHT. In addition, under the basal condition, UDA correlated positively with p-DOPA or the product of p-DOPA x Ccr, which might reflect the DOPA delivery at the renal proximal tubule. No significant difference was found in p-DOPA and the product of p-DOPA x Ccr among NT, NRH and LRH. However, the ratio of UDA/(p-DOPA x Ccr), which may indicate the conversion from DOPA to DA in the kidneys, was lower in EHT, especially in LRH, than that in NT. These results suggest that a reduced renal conversion from DOPA to DA may contribute to the attenuated natriuresis as well as renal dopaminergic activity in LRH.

[Physiological significance of plasma free and conjugated dopamine in healthy volunteers--with special reference to sympathetic nerve activity].

In order to elucidate the physiological significance of plasma dopamine, blood pressure, pulse rate (PR), plasma concentrations of free or conjugated dopamine (free or conjugated pDA), noradrenaline (pNA) and adrenaline (pAd) were measured in 9 healthy volunteers. Blood sampling for the measurements was performed at a basal condition maintaining a supine position for 60 minutes, after twenty minutes 60 degrees head-up tilt (tilt) and an intravenous infusion of 1000 ml 0.9% saline for 2 hours. Following tilt, mean values in diastolic and mean blood pressure, PR, pNA and pAd were significantly increased, while free, conjugated and total pDA were decreased. On the other hand, saline infusion yielded significant decreases in hematocrit, pNA, free, conjugated and total pDA, but blood pressure, PR and pAd remained at the same level. Free/conjugated pDA ratio did not change during tilt or saline infusion. The basal value of free, conjugated or total pDA did not significantly correlate with blood pressure, PR, pNA or pAd, respectively. Furthermore, no significant correlations between the changes in pDAs and hemodynamic parameters, pNA or pAd by tilt or saline infusion were observed. From these results, it was suggested that plasma free or conjugated dopamine in physiological conditions may not be released from sympathetic nerve endings or adrenomedullary glands. Further investigations are needed to clarify the physiological significance of plasma dopamine in humans.

The pathophysiological role of water-sodium balance and renal dopaminergic activity in overweight patients with essential hypertension.

Studies were conducted to evaluate the role of water-sodium balance and renal dopaminergic activity in the hypertensive mechanisms of overweight patients with essential hypertension (EHT). The body mass index (BMI) was correlated positively with mean arterial pressure, plasma volume, extracellular fluid volume, or total exchangeable sodium and negatively with plasma noradrenaline concentration or plasma renin activity in patients with EHT. Fractional excretion of sodium (FENa) was significantly lower in overweight patients than in normal weight patients with EHT. Hypotensive effect of sodium restriction or the natriuretic response to infused dopamine was more remarkable in overweight patients with EHT than in normal weight patients with EHT. Urinary excretion of free dopamine (UDA) was correlated positively with simultaneously measured urinary excretion of sodium or FENa and negatively with the natriuretic response to dopamine infusion. In addition, UDA was positively correlated with the BMI in normal weight patients with EHT, whereas the relation between the UDA and the BMI was significantly negative in overweight patients with EHT. These findings suggest that the expansion of body fluid volume and sodium might result from the blunted natriuretic ability due to an attenuation of the renal dopaminergic activity in overweight patients with EHT. The expansion of body fluid volume and sodium may play an important role in the hypertensive mechanisms of overweight patients with EHT.

The pathophysiological role of renal dopaminergic activity in patients with essential hypertension.

To evaluate the role of the renal dopaminergic system on renal water-sodium metabolism patients with essential hypertension (EHT), urinary excretion of dopamine, urinary excretion of sodium (UNaV) and fractional excretion of sodium (FENa) were all investigated before and after the administration of dopamine (3 micrograms/kg/min, intravenous infusion for 60 minutes), dopamine antagonist, metoclopramide (8 mg/m2 BSA, intravenous injection) or mild sodium loading in both normotensive subjects and benign EHT. In the basal values, no significant difference in urinary excretion of free (u-fDA), conjugated (u-cDA) or total dopamine (u-tDA) was found between normotensives and hypertensives. However, low renin EHT showed a pronounced reduction in u-fDA compared with normotensis subject and (NT) normal renin EHT. In this study, a significant reduction of u-cDA and of u-tDA was also found in those patients with low renin essential hypertension. In the normotensive and essential hypertensive groups UNaV or FENa showed a positive correlation with u-fDA (measured simultaneously), but not with u-tDA or u-cDA. The regression line between u-fDA and UNaV or FENa in EHT was shifted towards a lower u-fDA level than in NT. UNaV and FENa were increased by dopamine infusion and were decreased by metoclopramide injection in both NT and EHT. Changes of UNaV and FENa following dopamine or metoclopramide, showed a negative correlation with u-fDA measured immediately before the administration of these drugs. The enhanced natriuretic response to infused dopamine and the attenuated antinatriuretic response to injected metoclopramide were significant in low renin EHT, when compared with NT or normal renin EHT patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Interrelation between plasma kinin and the sympathetic nervous system in normal subjects.

To investigate the relationship between plasma kinin and the sympathetic nervous system, we measured plasma kinin, norepinephrine, and angiotensin-I-converting enzyme (ACE:kininase II) activity in normal subjects. In six normal subjects, subpressor and pressor doses of norepinephrine (10 ng/kg/min and 50 ng/kg/min, respectively) were infused for 1 hour. In five normal subjects, 60-degree head-up tilting was performed for 20 minutes. After norepinephrine infusion, plasma kinin levels were decreased significantly (p less than 0.01) with the subpressor dose of norepinephrine and were further decreased (p less than 0.01) with the pressor dose. Plasma ACE activity, however, showed no significant changes following these infusions. During the tilting, plasma kinin levels decreased significantly (p less than 0.01), whereas plasma norepinephrine levels increased significantly (p less than 0.01). From these results, the assumption of elevated levels in plasma endogenous or exogenous norepinephrine leads to a decrease in plasma kinin levels; this suggests that these two systems may be closely interrelated.

Plasma levels of human atrial natriuretic peptide in patients with hypertensive diseases.

Three types of antihuman atrial natriuretic peptide antiserum were obtained. From the study of cross-reactivity to human atrial natriuretic peptide fragments, it was suggested that antisera-1, -2, and -3 are mostly specific to 1-28, 5-25, and the ring structure, respectively. The estimated values of this hormone were significantly lower in the order of antisera-1, -2, and -3. Moreover, high performance liquid chromatographic study showed that various types of fragments of atrial natriuretic peptide exist in human plasma. These findings suggested that the highly specific antiserum to 1-28 human atrial natriuretic peptide such as antiserum-1 should be used to estimate the 1-28 human atrial natriuretic peptide levels in human plasma. From the study by using antiserum-1, it was concluded that the plasma human atrial natriuretic peptide increased in essential hypertensives, and in patients with primary aldosteronism, chronic renal failure, and malignant hypertension. Regarding the pathophysiological significance of increased plasma atrial natriuretic peptide, it is unlikely that this plays an important role in the etiology of essential hypertension or other hypertensive diseases, because the plasma level of this hormone is elevated in these patients. The increase of plasma atrial natriuretic peptide level in these patients should be considered to be a secondary or compensatory reaction to high blood pressure.

The pathophysiological role of water-sodium balance and renal dopaminergic activity in overweight patients with essential hypertension.

Studies were conducted to evaluate the role of water-sodium balance and renal dopaminergic activity in the hypertensive mechanisms of overweight patients with essential hypertension (EHT). The body mass index (BMI) was correlated positively with arterial pressure, plasma volume, extracellular fluid volume, or total exchangeable sodium and negatively with plasma noradrenaline concentration or plasma renin activity in patients with EHT. Fractional excretion of sodium (FENa) was significantly lower in overweight patients with EHT than that in normal-weight patients with EHT. Hypotensive effects of sodium restriction or the natriuretic response to infused dopamine was more remarkable in overweight than in normal-weight patients with EHT. Urinary excretion of free dopamine (UDA) was correlated positively with simultaneously measured urinary excretion of sodium or FENa and negatively with the natriuretic response to dopamine infusion. In addition, UDA was positively correlated with the BMI in normal-weight patients with EHT, whereas the relation between UDA and BMI was significantly negative in overweight patients with EHT. These findings suggest that the expansion of body fluid volume and sodium might result from the blunted natriuretic ability due to an attenuation of the renal dopaminergic activity in overweight patients with EHT. The expansion of body fluid volume and sodium may play an important role in the hypertensive mechanisms of overweight patients with EHT.