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Biomedical subjects

K Tsunoda

Publications and source records attributed to K Tsunoda.

At least 145 records · Page 8Linked to original sources
PubMed1987

Responses of vasoactive hormones in congestive cardiac failure.

Congestive cardiac failure causes activation of various neurohumoral responses that increase total peripheral resistance and promote salt and water retention. These effects increase blood pressure and organ perfusion in the short term, but ultimately cause further cardiac decompensation by increasing ventricular afterload and cardiac work. The role of the renin-angiotensin-aldosterone system and the catecholamines is partially understood, and blockade of these systems as a treatment of heart failure is now established. The role of vasopressin in heart failure is more controversial, but there is now compelling evidence that vasopressin may have important vasoconstrictor actions in addition to its fluid retaining properties. Atrial natriuretic factor is a newly described cardiac hormone released from the atrium. Atrial natriuretic factor causes natriuresis, diuresis, vasodilatation, suppression of thirst, and suppression of both renin and aldosterone. These actions largely counteract the effects of the renin-angiotensin system and vasopressin. Plasma atrial natriuretic factor has been reported to be markedly elevated in human and experimental heart failure, and may act to limit the neurohumoral response to reduced cardiac output. This review summarizes our understanding of the vasoactive hormones and reports experimental evidence supporting a pathophysiological role for vasopressin and atrial natriuretic factor in congestive cardiac failure.

Animals↗
PubMed1987

Role of endogenous angiotensin II and prostaglandins in the antihypertensive mechanism of angiotensin converting enzyme inhibitor in hypertension.

The role of endogenous angiotensin II and prostaglandins (PGs) in the antihypertensive effect of converting enzyme inhibitor, captopril, was studied in essential hypertension by the separate and the combined administration of captopril and indomethacin. Although plasma angiotensin II was similarly suppressed by the separate and the combined administration of captopril and indomethacin, captopril lowered and indomethacin increased the mean blood pressure. There were negative correlations between the changes in mean blood pressure and in urinary sodium excretion as well as in urinary PGE excretion. These results suggest that endogenous PGs may be implicated in the antihypertensive effect of captopril through the alteration of sodium balance.

Adult↗
PubMed1986

Effects of sodium and angiotensin II on urinary active and inactive kallikrein in rats.

To assess possible relationships between sodium balance, angiotensin II (ANG II), and renal active and inactive kallikrein, we studied the effects of sodium loading with 1% NaCl and chronic ANG II infusion (900 micrograms/kg per day) on the urinary excretion of total and active kallikrein for 6 days in conscious rats. We determined urinary total, active and inactive kallikrein by measuring kallikrein activity using a kininogenase assay before and after treatment with trypsin (200 micrograms/ml). Sodium loading produced a sustained increase in urinary total, active and inactive kallikrein excretion. Chronic infusion of ANG II induced a sustained increase in urinary total, active and inactive kallikrein excretion in rats on a regular diet. In rats loaded with sodium, however, ANG II did not induce any further changes in urinary kallikrein excretion. Thus, the present study suggests that both sodium loading and ANG II infusion might stimulate the synthesis of renal kallikrein. In addition, it is suggested that ANG II infusion might stimulate the synthesis of kallikrein, at least partly, via the same mechanism as sodium loading does.

Angiotensin II↗
PubMed1986

Effects of human atrial natriuretic peptide on renal function and vasopressin release.

To assess the effects of atrial natriuretic peptide (ANP) on the renal function, cardiovascular system, renin-angiotensin-aldosterone system, and vasopressin release, synthetic human ANP (alpha-hANP) was administered at a dose of 0.08 microgram X kg-1 X min-1 iv for 40 min into anesthetized dogs (n = 6). In the control study (n = 6), saline alone was infused. alpha-hANP brought about a significant increase in renal plasma flow, urinary Na and K output, urine flow, and osmolar clearance and a significant decrease in urinary osmolality, free water clearance, and filtration fraction (FF), with no changes in glomerular filtration rate. Plasma Na concentrations and osmolality did not change significantly, but plasma K concentrations fell progressively. Mean arterial blood pressure decreased without any changes in heart rate. Plasma renin activity (PRA), plasma aldosterone concentrations (PAC), and plasma vasopressin concentrations did not rise, but rather PRA and PAC tended to fall during alpha-hANP infusion. In the control study, there were no changes in these parameters except a progressive fall in FF and plasma K concentrations. These results indicate that the alpha-hANP-induced increase in renal blood flow plays an important role in producing natriuresis, but vasopressin may not be involved in the process of diuresis.

Aldosterone↗
PubMed1986

Role of the renal kinin-prostaglandin system in diltiazem-induced natriuresis.

Intravenous infusion of the Ca2+ entry blocker diltiazem (10 micrograms . kg-1 . min-1 for 30 min) induced an increase in urinary excretion of sodium (UNaV) from 209 +/- 42 to 922 +/- 311 mueq without significant alterations in renal hemodynamics in anesthetized rabbits. Urinary excretion of kinin (UkinV) and prostaglandin E (UPGEV) were also increased by diltiazem, from 14.3 +/- 2.5 to 25.9 +/- 4.8 ng and 1.33 +/- 0.20 to 2.44 +/- 0.34 ng, respectively. Moreover, there was a significant correlation between UkinV and UNaV (r = 0.81, P less than 0.05). A significant relationship between UPGEV and UNaV (r = 0.83, P less than 0.05) was also observed. However, no correlation between urinary excretion of kallikrein (UkallV) and UNaV was found after infusion of diltiazem. Further, to examine a possible contribution of renal kinins and prostaglandins in diltiazem-induced natriuresis, aprotinin (50,000 KIU/kg bolus + 1,000 KIU . kg-1 . min-1 infusion) and indomethacin (8 mg/kg) were used. Aprotinin pretreatment attenuated diltiazem-induced natriuresis, accompanied by suppression of UkallV, UkinV, and UPGEV. However, indomethacin pretreatment did not affect this drug-induced natriuresis, although UPGEV was significantly decreased. Furthermore, under the indomethacin pretreatment, a significant increase in UkinV was produced by diltiazem. These results suggest that renal kinins rather than renal prostaglandin E, at least in part, play a role in diltiazem-induced natriuresis.

Animals↗
PubMed1986

Atrial natriuretic peptide in chronic heart failure in the rat: a correlation with ventricular dysfunction.

To assess the relation between atrial natriuretic peptide and ventricular dysfunction, we simultaneously measured both atrial and plasma immunoreactive atrial natriuretic peptide concentrations in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. When compared to controls (n = 39), rats with infarction (n = 16) had markedly elevated plasma immunoreactive atrial natriuretic peptide concentrations (1205.8 +/- 180.9 vs. 126.7 +/- 8.9 pg/ml, p less than 0.001) and reduced immunoreactive atrial natriuretic peptide concentrations in right and left atria (31.4 +/- 4.6 vs. 61.2 +/- 3.2 ng/mg, p less than 0.001; 14.9 +/- 2.2 vs. 32.7 +/- 2.4 ng/mg, p less than 0.001, respectively). Right ventricular weight increased in proportion to infarct size, and both were correlated with plasma immunoreactive atrial natriuretic peptide levels (r = 0.825, p less than 0.001 and r = 0.816, p less than 0.001, respectively). Right atrial immunoreactive atrial natriuretic peptide content was significantly higher than left in both controls and rats with infarction. Both right and left atrial immunoreactive atrial natriuretic peptide concentrations were negatively correlated with both right ventricular weight as well as plasma immunoreactive atrial natriuretic peptide concentrations (right atrium: r = -0.816, p less than 0.001, r = -0.708, p less than 0.01; left atrium: r = -0.687, p less than 0.01, r = -0.644, p less than 0.01, respectively). These results suggest that chronic stimulation of atrial natriuretic peptide release from both atria is associated with increased turnover and depleted stores of atrial natriuretic peptide in atria in proportion to the severity of heart failure. It also suggests that plasma atrial natriuretic peptide levels may be used as a reliable index of cardiac decompensation in chronic heart failure.

Animals↗
PubMed1986

Effect of age on the renin-angiotensin-aldosterone system in normal subjects: simultaneous measurement of active and inactive renin, renin substrate, and aldosterone in plasma.

To investigate the effect of aging on the renin-angiotensin-aldosterone system, plasma renin substrate concentrations (PRSC); plasma total, active, and inactive renin concentrations (TRC, ARC, and IRC); PRA; and plasma aldosterone concentrations (PAC) were measured simultaneously in 60 normal subjects, 18-84 yr old. PRSC was measured by the addition of excess human renal renin. ARC and TRC after trypsin activation were measured by adding sheep renin substrate; IRC was calculated by subtracting ARC from TRC. The active renin ratio was calculated as follows: ARC/TRC X 100%. PRA and PAC were measured by RIA. There were no significant changes in PRSC, TRC, IRC, and PRA to PAC ratio with aging. Both ARC and active renin ratio fell significantly with aging (r = 0.46 and P less than 0.01; and r = 0.54 and P less than 0.01, respectively). PRA and PAC also tended to decrease with aging (r = 0.35 and P less than 0.01; and r = 0.59 and P less than 0.01, respectively). A significant positive correlation was found between PRA and ARC (r = 0.72; P less than 0.001). PRA was also correlated with PAC. In conclusion, the age-related decrease in PRA is not due to the change in PRSC, but is mainly due to the fall in ARC. Decreased conversion of inactive to active renin might be responsible in part for the reduced ARC in the elderly.

Adolescent↗
PubMed1986

The changes in active and inactive renin induced by various maneuvers in hypertensive patients.

The changes in active and inactive renin after captopril (n = 29) or furosemide administration (n = 10) were studied in hypertensive patients. Furthermore, after percutaneous transluminal angioplasty (PTA) in 3 cases of renovascular hypertension (RVH), and after nephrectomy in a case of juxtaglomerular cell tumor, the time course of the changes in these two types of renin was investigated. Inactive renin was activated by trypsin treatment. Plasma renin concentration was measured by using an excess of sheep substrate. In patients with essential hypertension or primary aldosteronism, inactive renin was unchanged, irrespective of response in active renin, after the administration of captopril and furosemide. In patients with RVH, inactive renin was markedly decreased by furosemide but unchanged by captopril, in spite of significant increase in active renin. After PTA and nephrectomy, inactive renin decreased slower than active renin. These data support the idea that in patients with RVH, the increase in active renin by furosemide is at least partly due to the activation of inactive renin. It is also suggested that the increase in active renin by captopril is mainly due to the promoted release of active renin from the kidney. Furthermore, it seems likely that the metabolic clearance of inactive renin is slower than that in active renin.

Administration, Oral↗
PubMed1986

Hypotensive and natriuretic effects of nifedipine in essential hypertension. Role of renal kallikrein-kinin-prostaglandin and renin-angiotensin-aldosterone systems.

To assess the role of renal kallikrein-kinin-prostaglandin and renin-angiotensin-aldosterone systems in the diuretic and natriuretic actions of nifedipine, a calcium-channel blocker, 20 mg of nifedipine was administered orally to 15 patients with essential hypertension. Nifedipine promptly induced a hypotensive effect and an increase in pulse rate. Urine volume, urinary sodium excretion, and creatinine clearance were significantly increased after the administration of nifedipine by 63.5%, 48.5% and 12.4%, respectively. Urinary excretion of kallikrein and prostaglandin E were also significantly increased after the administration of nifedipine by 29.4% and 50.0%, respectively. The change in urinary kallikrein excretion was significantly correlated with that in urine volume (r = 0.70, p less than 0.01) or that in urinary sodium excretion (r = 0.86, p less than 0.01). In addition, the change in urinary prostaglandin E excretion was also significantly correlated with that in urine volume (r = 0.72, p less than 0.01) or that in urinary sodium excretion (r = 0.53, p less than 0.05). Plasma aldosterone concentration did not change despite of the marked increase in plasma renin activity, and plasma aldosterone concentration/plasma renin activity ratio decreased after the administration of nifedipine. These results suggest that the augmented renal kallikrein-kinin-prostaglandin system and the suppressed secretion of aldosterone may be associated with the diuretic and natiuretic action of nifedipine and may contribute to the reduction in blood pressure that is caused mainly by its vasodilatory action.

Adult↗
PubMed1985

Atrial natriuretic factor inhibits the hypertension induced by chronic infusion of norepinephrine in conscious rats.

To assess the physiological role of atrial natriuretic factors in the regulation of blood pressure and sodium-water excretion, we studied the chronic effects of continuous infusion of a synthetic atrial natriuretic factor of 25 amino acids for up to 3 days on systolic blood pressure, urine volume, and urinary excretion of sodium, prostaglandin E2 and kallikrein in conscious rats, and also evaluated the antihypertensive effect of this substance in rats with hypertension caused by chronic infusion of norepinephrine. Continuous infusion of atrial natriuretic factor (150 micrograms/kg per day) into the jugular vein via osmotic minipumps did not induce any changes in systolic blood pressure, urine volume, and urinary excretion of sodium, prostaglandin E2, and kallikrein for up to 3 days, compared with those in vehicle-infused rats. When the same dose of atrial natriuretic factor was administered simultaneously with 1.8 mg/kg per day of norepinephrine infused intraperitoneally by osmotic minipumps, the systolic blood pressure of conscious rats rose on day 1 to only 127.3 +/- 6.3 mm Hg compared with the rise to 146.3 +/- 1.6 mm Hg when norepinephrine alone was infused (P less than 0.05). The antihypertensive effect of atrial natriuretic factor was sustained for 3 days in rats infused with norepinephrine. The administration of atrial natriuretic factor to rats made hypertensive by 3 days of infusion with norepinephrine alone returned the blood pressure to control levels, and the antihypertensive effect was sustained throughout the experimental period lasting for 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Active, inactive and total renin concentrations in plasma of hypertensive patients.

To assess the role of inactive renin in hypertensive patients, active, inactive and total renin concentrations (ARC, IRC and TRC) were measured in 37 patients with hypertension of various etiologies. Inactive renin was activated by trypsin and renin concentration was measured using an excess of sheep substrate. Mean values of ARC, IRC, TRC and active renin ratio (AR ratio = ARC/TRC) were higher in 6 cases of renovascular hypertension, and lower in 6 cases of primary aldosteronism and 1 case of idiopathic hyperaldosteronism, when compared with 59 cases of normal subjects. Between ARC and IRC, a slightly positive correlation was observed. Moreover, between ARC and TRC as well as between ARC and AR ratio, close positive correlations were observed. Exceptionally, in a case of juxtaglomerular cell tumor, AR ratio was low in spite of the extremely high value of ARC. Our data suggest that the increase in circulating active renin is due to both the enhancement of the release of renin from the kidney and the increase in the activation of inactive renin, and vice versa.

Adolescent↗