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Biomedical subjects

H Rakugi

Publications and source records attributed to H Rakugi.

88 records · Page 5Linked to original sources
PubMed1989

Endothelin inhibits presynaptic adrenergic neurotransmission in rat mesenteric artery.

The effect of endothelin(ET) on adrenergic neurotransmission was examined in isolated perfused rat mesenteric arteries. Porcine ET(10(-12) to 10(-10)M) attenuated the pressor response to sympathetic nerve stimulation (NS). It also stimulated the release of prostaglandin E2 (PGE2), but its inhibition of the pressor response to NS was not affected by indomethacin treatment. ET also caused dose-dependent inhibition of [3H]norepinephrine release during NS. Higher doses of ET rather enhanced the pressor response to NS. These results suggest that ET inhibits presynaptic adrenergic neurotransmission without mediation of PGE2, while it potentiates the responsiveness of the postsynaptic alpha-adrenergic receptor. Thus ET appears to act directly on the neuroeffector junction as well as on the peripheral vasculature.

Adrenergic Fibers↗
PubMed1989

Endothelin stimulates the release of prostacyclin from rat mesenteric arteries.

The effect of endothelin on the release of prostacyclin was examined in perfused rat mesenteric arteries with or without their pretreatment with indomethacin. Porcine endothelin at 10 pmol (a subpressor dose) and 40 pmol stimulated the release of 6-keto-PGF1 alpha, a stable metabolite of prostacyclin. Rat endothelin also stimulated its release, but less than porcine endothelin. Pretreatment with indomethacin completely inhibited this 6-keto-PGF1 alpha release. These results indicate that endothelin stimulates the release of prostacyclin from mesenteric arteries. This release may modulate the action of endothelin locally.

Animals↗
PubMed1989

Endothelin enhances adrenergic vasoconstriction in perfused rat mesenteric arteries.

The interaction of endothelin with alpha-adrenergic receptors was examined in isolated perfused rat mesenteric arteries. Infusion of porcine or rat endothelin increased the baseline perfusion pressure dose-dependently. Subpressor doses of both porcine (10(-11) and 10(-10)M) and rat (10(-10) and 10(-9)M) endothelin enhanced the pressor responses to norepinephrine. Nicardipine (10(-7)M), a calcium channel blocker, attenuated this potentiation. These results suggest that endothelin enhances the responsiveness of alpha-adrenergic receptors to catecholamines probably through the increase in calcium influx. Thus endothelin may interact with sympathetic nerve activity in addition to having a direct vasoconstrictor action in peripheral vascular tissue.

Animals↗
PubMed1989

Actions of endothelin on adrenergic neuroeffector junction.

The effect of endothelin, a novel vasoconstrictor peptide, on the adrenergic neuroeffector junction was investigated in isolated perfused rat mesenteric arteries. The vasoconstrictor responses to periarterial nerve stimulation and exogenous noradrenaline were determined. Infusion of endothelin-1 (10(-14) to 10(-8) mol/l) increased the baseline perfusion pressure dose dependently. Subpressor doses of endothelin-1 (10(-11) and 10(-10) mol/l) enhanced the pressor response to noradrenaline, and 10(-12) to 10(-10) mol/l endothelin-1 attenuated the pressor response to periarterial nerve stimulation. Endothelin-1 also caused a dose-dependent inhibition of [3H]-noradrenaline release during the periarterial nerve stimulation. However, higher doses of endothelin-1 (3 x 10(-10) to 10(-8) mol/l) enhanced the pressor response to stimulation. These results suggest that endothelin potentiates adrenergic vasoconstriction postjunctionally while it inhibits adrenergic neurotransmission. Thus endothelin may have actions on the neuroeffector junction in addition to its direct vasoconstricting effect.

Animals↗
PubMed1989

Renal interaction of atrial natriuretic peptide with angiotensin II: glomerular and tubular effects.

1. The possible interactions between the renal effects of atrial natriuretic peptide (ANP) and angiotensin II (AII) were studied in normal sodium-replete human subjects. Recent investigations have suggested that ANP inhibits the pressor and volume-retaining effects of activation of the renin-angiotensin system. Thus, ANP may attenuate the effects of AII on renal haemodynamics or tubular transport. 2. ANP (0.1 micrograms/kg per min, 60 min) was intravenously infused into eight normal human subjects with and without pretreatment with enalapril (20 mg, per oral), an inhibitor of the converting enzyme, and during infusion of AII (10 mg/kg per min). 3. ANP infusion alone caused increases in the urine volume (from 96 +/- 23 to 229 +/- 44 mL/h, P less than 0.05) and urinary sodium excretion (from 11.5 +/- 1.6 to 20.9 +/- 4.2 mEq/h, P less than 0.05). These changes were accompanied by an increase in the glomerular filtration rate (from 127 +/- 9 to 158 +/- 9 mL/min, P less than 0.05). ANP infusion after enalapril administration lowered the mean blood pressure (from 76 +/- 2 to 71 +/- 3 mmHg, P less than 0.05) to a level similar to that observed during ANP infusion alone (from 84 +/- 2 to 74 +/- 2 mmHg, P less than 0.01), but did not result in a significant diuresis (from 139 +/- 23 to 174 +/- 51 mL/h) or natriuresis (from 19.7 +/- 2.5 to 14.3 +/- 3.4 mEq/h, P less than 0.05). This combined treatment with a converting enzyme inhibitor and ANP reduced both the glomerular filtration rate (160 +/- 9 to 141 +/- 10 mL/min) and the renal plasma flow (from 775 +/- 49 to 570 +/- 45 mL/min, P less than 0.01). 4. The antinatriuretic effects of exogenous AII were reversed by superimposed ANP infusion (urinary sodium excretion: from 4.8 +/- 1.0 to 24.3 +/- 5.2 mEq/h, P less than 0.01). Under these conditions, the glomerular filtration rate increased (from 114 +/- 6 to 156 +/- 7 mL/min, P less than 0.05) to levels similar to those observed with ANP infusion alone. In addition the increased tubular sodium reabsorption induced by AII was inhibited by concomitant ANP infusion (fractional proximal tubular sodium reabsorption: from 90.7 +/- 3.5 to 80.3 +/- 16.6%, P less than 0.05, fractional post-proximal tubular sodium reabsorption: from 91.5 +/- 9.8 to 87.6 +/- 8.8%, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Renin inhibitor and converting enzyme inhibitors suppress vascular angiotensin II.

The direct effects of a renin inhibitor, N-acetyl-pepstatin and five angiotensin converting enzyme inhibitors, captopril and the active diacid forms of enalapril, ramipril, cilazapril, and CS-622, on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries. Vascular renin activity and angiotensin II (Ang II) released into the perfusate were determined. Infusion of N-acetyl-pepstatin (5 X 10(-8)-5 X 10(-6) M) suppressed vascular renin activity and Ang II release dose dependently. Isoproterenol (10(-6) M) induced a 135 +/- 30% increase in Ang II release from the basal value. N-Acetyl-pepstatin (5 X 10(-6) M) suppressed isoproterenol-induced Ang II release. Infusions of 5 X 10(-6) M captopril and the diacid forms of enalapril, ramipril, cilazapril, and CS-622 by themselves had little effect on Ang II release, but concomitant infusion of isoproterenol with these angiotensin converting enzyme inhibitors significantly decreased Ang II release (71 +/- 21%, 51 +/- 40%, 8 +/- 21%, 69 +/- 24%, and 44 +/- 29% increase, respectively, from the basal values). These results indicate that N-acetyl-pepstatin suppresses the vascular renin-angiotensin system. This effect may in part contribute to the hypotensive actions of renin inhibitors. Although angiotensin converting enzyme inhibitors also suppress locally generated Ang II, the mechanism and physiological significance still remain to be clarified.

Angiotensin II↗
PubMed1989

Effect of atrial natriuretic peptide on catecholamine release from human pheochromocytoma.

The effect of synthetic alpha human atrial natriuretic peptide on catecholamine release from human pheochromocytomas was studied both in vivo and in vitro. Iv infusion of atrial natriuretic peptide at a rate of 0.1 microgram.kg-1.min-1 for 60 min into two normotensive patients with pheochromocytoma caused a small decrease in the mean blood pressure, increase in the heart rate, and marked increase in the plasma level of norepinephrine (2.08 to 6.83 nmol/l, and 1.15 to 2.83 nmol/l, respectively) compared with 0.60 +/- 0.10 to 1.19 +/- 0.20 nmol/l in normal subjects. Treatment with atrial natriuretic peptide also increased the plasma epinephrine level from 0.34 to 1.27 nmol/l, and from 0.67 to 0.79 nmol/l in the patients with pheochromocytoma, but not in the normal subjects (0.05 +/- 0.01 to 0.05 +/- 0.01 nmol/l). After removal of the tumour, the responses of the plasma norepinephrine and epinephrine to atrial natriuretic peptide infusion were normalized. There was no significant effect of 10(-8) to 10(-5) mol/l atrial natriuretic peptide on the basal release of catecholamines from isolated superfused pheochromocytoma tissue. Atrial natriuretic peptide (10(-7) mol/l) did not affect the increase in catecholamine release induced by glucagon (10(-5) mol/l). These results suggest that the exaggerated responses of plasma catecholamines to atrial natriuretic peptide in patients with pheochromocytoma may be due to a washout effect resulting from change in blood flow in the vessels feeding the tumour rather than increased sympathetic nerve activity induced by hypotension and hypovolemia. The results also suggest that atrial natriuretic peptide dose not have any direct action on pheochromocytoma tissue causing catecholamine release.

Adrenal Gland Neoplasms↗
PubMed1989

Role of angiotensin II in the renal response to atrial natriuretic peptide in normal subjects.

Atrial natriuretic peptide (ANP) has been shown to inhibit angiotensin II (Ang II)-induced steroidogenesis and vasoconstriction. To investigate the role of Ang II in the renal response to ANP, a synthetic ANP (0.1 micron/kg/min, 60 min) was infused for 1 h in eight subjects with or without pretreatment with an inhibitor of the converting enzyme, enalapril (20 mg, p.o.), or Ang II (10 ng/kg/min). ANP infusion alone caused increases in urinary volume, urinary sodium excretion, and glomerular filtration rate (GFR). However, enalapril treatment abolished these diuretic and natriuretic effects of ANP. In this group, GFR was decreased and no tubular effects, which was estimated by urinary excretion of sodium and phosphate, were observed. The anti-natriuretic effects of exogenous Ang II were reversed by concomitant ANP infusion, which inhibited both proximal and postproximal sodium reabsorption induced by Ang II without changing the GFR. These results indicate that endogenous Ang II plays an obligatory role in the natriuretic response to ANP and also suggested that ANP inhibits Ang II-stimulated tubular reabsorption of sodium.

Adult↗
PubMed1988

Endothelin inhibits renin release from isolated rat glomeruli.

The effect of endothelin on renin release from isolated rat glomeruli was examined. Endothelin inhibited basal renin release in a dose-dependent manner with an IC50 of 1.0 x 10(-9) M. Endothelin also inhibited renin release stimulated by isoproterenol (10(-5) M). Nifedipine (10(-5) M), a calcium channel blocker, induced an increase in renin release. Endothelin did not affect this nifedipine-induced renin release. These results suggest that endothelin inhibits renin release via a calcium entry mechanism and increases intracellular calcium.

Animals↗
PubMed1988

Changes in the levels of plasma atrial natriuretic peptide, hemodynamic measurements, and the levels of vasoactive hormones during the clinical course of congestive heart failure.

To investigate the mechanism for the release of human atrial natriuretic peptide (hANP) and the pathophysiological role of hANP in patients with congestive heart failure (CHF), plasma hANP levels in patients with dilated cardiomyopathy (DCM) or acute myocardial infarction (AMI) were determined serially, and the relationship between plasma ANP levels and hemodynamic measurements or various vasoactive hormones was analyzed during the clinical course of congestive heart failure. In 63 patients with either AMI or DCM, plasma hANP, plasma renin activity, aldosterone concentration, and catecholamines were measured over 4 weeks, during the course of CHF. Cardiac catheterization with a Swan-Ganz catheter was also performed. Plasma hANP in patients with DCM was elevated continuously during the clinical course. Plasma hANP levels in patients with AMI of Groups II and IV of Forrester's class decreased on days 7 and 14 and those in patients with AMI of Group I changed within normal limits. Plasma hANP levels were correlated positively with pulmonary artery pressure and pulmonary capillary wedge pressure in patients with AMI or DCM. Plasma renin activity, noradrenaline, and adrenaline levels were elevated in the acute phase of myocardial infarction and had a tendency to decrease upon improvement in clinical status. Plasma renin activity and noradrenaline level correlated positively with plasma hANP levels. These data indicate that plasma hANP levels are regulated by atrial distension and severity of cardiac impairment, and that plasma hANP and plasma renin activity or catecholamines correlated closely during the clinical course of CHF, indicating that these hormones may be involved in the volume and electrolytes status in CHF.

Adult↗
PubMed1988

Effect of vasodilator prostaglandins on the vascular renin-angiotensin system.

The interaction of prostaglandin (PG) with the vascular renin-angiotensin (R-A) system was examined by studies on the effects of PGI2, PGE2 and the inhibitor of PG synthesis, indomethacin, on the release of angiotensin II (Ang II) from isolated rat mesenteric arteries. The Ang II released from the vasculature was measured after its concentration in a Sep-Pak C18 cartridge connected to the perfusion system. After perfusion with drugs, the specific vascular renin activity inhibited by anti-renin antibody was determined. The basal perfusion pressure was constant (19.6 +/- 1.1 mmHg) at a flow rate of 4.5 ml/min, and was not changed by any of these drugs. The basal levels of Ang II release and vascular renin activity were 44 +/- 5 pg/30 min and 113 +/- 8 pg Ang I/mg protein/hr, respectively. Infusion of PGI2 (10(-6) M) significantly decreased both Ang II release (p less than 0.01) and vascular renin activity (p less than 0.05) as compared with the control levels. Infusion of PGE2 (10(-6) M) decreased Ang II release significantly (p less than 0.05) and vascular renin activity slightly. Infusion of indomethacin (10(-6)M) increased vascular renin activity significantly (p less than 0.01). Pretreatment with indomethacin (10 mg/kg, ip) for 2 days also increased vascular renin activity (p less than 0.01). These results indicate that in contrast to their effects on the renal R-A system, PGs suppress the vascular R-A system and that these two local vasoactive factors interact to regulate vascular tone.

Angiotensin II↗
PubMed1988

Interaction between the vascular renin-angiotensin system and prostaglandins.

The effects of nephrectomy, prostacyclin (PGI2), prostaglandin E2 (PGE2) and indomethacin on the vascular renin-angiotensin system were examined using isolated perfused mesenteric arteries. Angiotensin II (Ang II) released from the vasculature was measured using a Sep-Pak C18 cartridge which was placed in the perfusion system. After perfusion with drugs, the specific vascular renin activity inhibited by antirenin antibody was determined. Plasma renin activity was markedly decreased 48 h after nephrectomy, whereas vascular renin activity was increased. Released Ang II from mesenteric arteries of nephrectomized rats was not significantly different from that in control rats. Infusion of PGI2 (10(-6) mol/l) and PGE2 (10(-6) mol/l) for 1 h caused significant decreases in Ang II release (P less than 0.01 and P less than 0.05, respectively) and also decreased vascular renin activity. In contrast, infusion of indomethacin (10(-6) mol/l) for 1 h resulted in an increase (P less than 0.01) in vascular renin activity. These findings suggest that the vascular renin-angiotensin system exists independently of the circulating renin-angiotensin system. In contrast with their effects on renal renin, prostaglandins suppress the vascular renin-angiotensin system. The interaction between two vasoactive hormones in the vascular wall may be important for local regulation of vascular tone and regional blood flow.

Angiotensin II↗
PubMed1987

Plasma atrial natriuretic peptide level as an index for the severity of congestive heart failure.

Human atrial natriuretic peptide (hANP) is a vasodepressor and a natriuretic hormone. The levels of plasma hANP increase during extracellular volume expansion. In the present study, we investigated whether plasma levels of hANP were associated with the severity of congestive heart failure (CHF), and whether such an association could be used as a diagnostic aid. Plasma hANP levels in 102 patients with various heart diseases and correlation between the plasma hANP levels and the left ventricular ejection fraction (EF) determined from echocardiography in 43 patients were examined. The plasma levels of hANP were high during the state of extracellular fluid overloading and atrial distention as determined by high right atrial pressure and pulmonary capillary wedge pressure. The high plasma hANP levels decreased in CHF patients whose clinical state improved, but remained high in those patients who were refractory to treatment. Plasma hANP levels correlated inversely with left ventricular EF (r = -0.41, p less than 0.01). In 9 patients reexamined during the course of treatment the plasma hANP levels decreased with an increase in EF. These data indicate that the level of plasma hANP is a practical diagnostic indicator of the severity of CHF, and can also be used as a means for assessing the efficacy of the treatment.

Adult↗
PubMed1987

Hemodynamic, renal, and hormonal responses to alpha-human atrial natriuretic peptide in patients with congestive heart failure.

Hemodynamic, renal, and hormonal effects of intravenous bolus injection of 50 micrograms synthetic alpha-human atrial natriuretic peptide (alpha-hANP) were studied in eight patients with congestive heart failure. alpha-hANP caused significant reductions in mean blood pressure and systemic vascular resistance. These responses were sustained up to 90 minutes and not accompanied by reflex tachycardia. Cardiac index and stroke volume index increased significantly at 90 minutes and pulmonary capillary wedge pressure, pulmonary arterial pressure, and mean right atrial pressure remained unchanged. Urine volume, urinary sodium excretion, creatinine clearance, and fractional excretion of sodium increased significantly, but fractional excretion of potassium and phosphate did not change. Elevated plasma renin activity, plasma aldosterone, and norepinephrine were suppressed after the injection of alpha-hANP. The bolus injection of this peptide has moderately hypotensive, vasorelaxant, and natriuretic effects in patients with congestive heart failure.

Aged↗