Biomedical subjects

M Nakamaru

Publications and source records attributed to M Nakamaru.

At least 55 records · Page 3Linked to original sources

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↗

PubMed1989

Changes in plasma active renin and prorenin after endoscopic retrograde pancreatography.

Plasma active renin, total renin (active renin plus prorenin) and immunoreactive trypsin were measured simultaneously before and after endoscopic retrograde pancreatography (ERP) in 9 subjects suspected of having pancreatic or biliary disease. After ERP, their plasma immunoreactive trypsin level increased significantly (p less than 0.02) from 12.4 +/- 1.5 to 163 +/- 57 ng/ml (means +/- SEM), while their plasma renin activity, total renin activity and ratio of active renin to total renin did not change. Individual values for the ratio of active renin to total renin correlated significantly (p less than 0.01) with those for immunoreactive trypsin in the basal condition (before ERP), but not after ERP. These results suggest that plasma trypsin is involved in activation of prorenin to active renin in the basal condition, and that ERP-induced increase in plasma trypsin has no effect on activation of prorenin.

Blood Pressure↗

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

The renin-angiotensin system: an overview of its intracellular function.

The enzyme renin has been purified and characterized by structural analysis. Pure renin protein was used to produce a specific antibody to renin, which was useful in demonstrating the presence of a specific renin in many tissues other than kidney. Further, in these cells angiotensins I and II and converting enzyme all were found to coexist with renin by immunohistochemical studies, indicating the local production of renin, angiotensinogen and angiotensins in these cells. Angiotensin II produced in the cultured cells was secreted to the outside of the cells. Secretion of angiotensin II from the angiotensin-producing cells was demonstrated with perfused mesenteric artery. The secretion of angiotensin II from the vascular beds was inhibited by converting enzyme inhibitors, and was stimulated by the adrenergic beta-agonist isoproterenol. These studies demonstrate local production and controlled secretion of angiotensin II and define its physiologic role.

Angiotensin II↗

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

Conceptual evolution of renin research.

Research on renin in the last 90 years has undergone numerous conceptual evolution since its discovery by Tigerstedt and Bergman in 1898. This paper briefly reviews the evolutionary steps leading up to the recently discovered intracellular function of renin and generation of angiotensin II in renin containing cells and molecular biological studies approaching the regulation of renin expression in various tissues.

Animals↗

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↗

PubMed1988

Local generation and release of angiotensin II in peripheral vascular tissue.

Isolated rat hindlegs were perfused with Krebs-Ringer solution, and immunoreactive angiotensin II (irAng II) released into the perfusate was directly determined using a Sep-Pak C18 cartridge connected to the perfusion system. High performance liquid chromatography clearly demonstrated the presence of angiotensin I (Ang I), angiotensin II (Ang II), and a small amount of angiotensin III. The spontaneous release of irAng II was as high as about 600 pg/30 min, which was stable up to 3 hours. Captopril added to the perfusion medium (10(-9) to 10(-6) M) suppressed irAng II release in a dose-dependent manner (p less than 0.001), and it (10(-6)M) caused a reciprocal increase of irAng I release (p less than 0.05). Oral pretreatment of captopril (50 mg/kg/day) for 1 week suppressed the irAng II release by 31% (p less than 0.02). The same treatment with SA 446, a highly lipophilic angiotensin converting enzyme inhibitor, inhibited the irAng II release by 63% (p less than 0.001). On the other hand, the two inhibitors suppressed the plasma irAng II to very similar extents. Pretreatment with SA 446 plus nephrectomy did not cause any further change in irAng II release as compared with that with SA 446 alone. These results provide direct proof for local generation and subsequent secretion of Ang II by peripheral vascular tissue.

3-Mercaptopropionic Acid↗

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↗

PubMed1987

Effect of captopril on angiotensin II release from vascular tissues in rats.

Isolated rat hindlegs were perfused with Krebs-Ringer solution and released angiotensin I (ANG I) and ANG II were determined. The release of ANG I and ANG II in nephrectomized rats did not differ from those in control group. Pretreatment with captopril (50 mg/kg/day) for 3 days or addition of captopril (2 X 10(-6) M) to the perfusate induced increase in ANG I release and decrease in ANG II release. These findings suggest that ANG II is locally generated and release from the vascular tissues. Captopril may inhibit the conversion of vascular ANG I into ANG II.

Angiotensin I↗

PubMed1986

Atrial natriuretic factor inhibits norepinephrine release evoked by sympathetic nerve stimulation in isolated perfused rat mesenteric arteries.

The effect of atrial natriuretic factor (ANF) on [3H]norepinephrine release evoked by sympathetic nerve stimulation was examined in the isolated perfused rat mesenteric arteries. ANF (1 nM to 0.1 microM) caused a dose-dependent inhibition of [3H]norepinephrine release during nerve stimulation. The present result indicates that ANF inhibits noradrenergic neurotransmission in the rat mesenteric arteries through a prejunctional mechanism. This prejunctional effect of ANF may in part contribute to its vasodilation action.

Animals↗

PubMed1986

Role of vascular angiotensin II released by beta-adrenergic stimulation in rats.

The effect of a beta-adrenoceptor agonist on the release of the components of the vascular renin-angiotensin system was examined in vitro. Isolated rat mesenteric arteries were perfused in an open system with Krebs-Ringer solution and released immunoreactive angiotensin II (ANG IIir) into the perfusate was directly determined using a Sep-Pak C-18 cartridge connected to the perfusion system. Renin activity in the concentrated perfusate was also determined. Isoproterenol (1 nM-1 microM) increased the release of ANG IIir in a dose-dependent manner. The increase in ANG IIir release during isoproterenol (1 microM) infusion was inhibited by propranolol (1 microM) or captopril (2 microM). Isoproterenol-induced increment of ANG IIir release was blocked by the selective beta 2-adrenoceptor antagonist, ICI 118,551 (1 microM), but not by the selective beta 1-adrenoceptor antagonist, atenolol (1 microM). Renin activity in the perfusate was measurable, but did not increase in response to isoproterenol (1 microM) infusion. There was no significant difference in the response of ANG IIir release to isoproterenol between spontaneously hypertensive rats and Wistar-Kyoto rats. The present results indicate that locally generated ANG II is released by beta 2-adrenoceptor activation. The beta-adrenoceptor agonist and the vascular renin-angiotensin system may play an important role for the regulation of peripheral vascular tone.

Adrenergic beta-Antagonists↗

PubMed1986

Beta-adrenoceptor-mediated release of angiotensin II from mesenteric arteries.

Essential components of the renin-angiotensin system such as renin enzymes, angiotensinogen, converting enzyme, and angiotensin receptors have been found in vascular tissues. Locally generated angiotensin (ANG) II may regulate vascular tone by contracting vascular smooth muscle or potentiating sympathetic activity. Recently it was suggested that beta-adrenoceptor-induced enhancement of noradrenergic neurotransmission is mediated by the vascular renin-angiotensin system. The present study was designated to obtain direct evidence for the release of ANG II from the vasculature by beta-adrenoceptor activation. Isolated rat mesenteric arteries were perfused in vitro with Krebs-Ringer solution, and released ANG II was concentrated in a Sep-Pak C-18 cartridge connected to the perfusion system. High-pressure liquid chromatography combined with radioimmunoassay clearly demonstrated the presence of ANG I, II, and a small amount of ANG III in the perfusate. Isoproterenol (10(-9) - 10(-6) M) induced the enhancement of pressor responses to nerve stimulation. This effect was markedly suppressed by propranolol (5 X 10(-7) M), captopril (2 X 10(-6) M), or [Sar1-Ile8]ANG II (10(-6) M). Isoproterenol (10(-9) - 10(-6) M) caused increase in the release of ANG II from mesenteric arteries. The increase in ANG II release during isoproterenol (10(-6) M) infusion was blocked by propranolol (10(-6) M). Captopril (2 X 10(-6) M) also inhibited the increase in ANG II induced by isoproterenol. These results indicate that locally generated ANG II is released from isolated perfused rat mesenteric arteries and its release is mediated by beta-adrenoceptors.

Angiotensin II↗

PubMed1986

Intracellular action of renin, angiotensin production and release.

The enzyme renin has been purified and characterized by structural analysis. Pure renin protein was used to produce a specific antibody to renin, which was useful in demonstrating the presence of a specific renin in many tissues other than kidney. In these cells angiotensins I and II and angiotensin converting enzyme were found to coexist with renin by immunohistochemical studies and by the direct determination with cultured cells. Studies with these cells indicated the local production of renin, angiotensinogen and angiotensins in these cells. Angiotensin II produced in the cultured cells was secreted to the outside of the cells while more than 95% renin remained within the cells. Secretion of angiotensin II from the angiotensin producing cells was demonstrated with perfused mesenteric artery. The secretion was stimulated by the adrenergic beta-agonist isoproterenol in a dose-dependent manner and specifically inhibited by a beta 2-antagonist. Angiotensin II secreted from the vascular bed by the beta 2-adrenoceptor stimulation acts locally to facilitate norepinephrine release. These studies demonstrate local production and secretion of angiotensin II and define its physiological role.

Angiotensin II↗

PubMed1985

Evidence for existence of angiotensins I and II in mature renin granules from rat kidney cortex.

Renin granules were isolated by the combination of discontinuous and continuous Percoll density gradient centrifugation. The peak fraction containing the highest concentration of renin granules was found to contain the highest concentration of both angiotensin I and II immunoreactive substances. The identity of the immunoreactive peptides was further confirmed as angiotensin I and angiotensin II by high pressure liquid chromatography in reference to standard compounds. The coexistence of angiotensins I and II with renin indicates the formation of angiotensin II in renin granules. These findings clarify the mechanism of intracellular formation of angiotensin II as opposed to its formation in plasma and provide evidence against the internalization of angiotensin II, a hypothesis supported by the failure to detect angiotensin I in renin granules. Angiotensin II was increased by a low sodium diet while a high sodium diet did not affect its content.

Angiotensin I↗

PubMed1985

A role for the adrenal renin-angiotensin system in the regulation of potassium-stimulated aldosterone production.

Potassium is a major regulator of aldosterone production. It also increases adrenal renin. The causal relationship between potassium and adrenal renin is not known. To evaluate the role of the intraadrenal renin-angiotensin (ANG) system in potassium-stimulated aldosterone synthesis and release, specific adrenal renin activity, PRA, and plasma aldosterone were measured during potassium loading or captopril treatment in the rat. Adrenal ANGs were determined using a HPLC system combined with RIA to obtain quantitative information on the components of the adrenal renin-ANG system. In addition, the effect of pretreatment with captopril on aldosterone production by isolated adrenal glomerulosa cells was examined. In intact animals potassium loading markedly increased adrenal renin and plasma aldosterone, whereas PRA was suppressed. The administration of captopril to rats in normal potassium balance did not suppress plasma aldosterone. Captopril treatment during potassium loading inhibited the potassium-induced increase in aldosterone. Furthermore, pretreatment with captopril suppressed adrenal ANG II and reduced the response of aldosterone production to extracellular potassium concentration by isolated adrenal glomerulosa cells in vitro. These results suggest that the adrenal renin-ANG system plays a significant role in the control of aldosterone production under potassium stimulation.

Adrenal Glands↗

PubMed1984

Synergic effects of kallikrein-kinin and prostaglandins on renin release on infusion of isolated hog kidney with aldosterone.

The effects of infusion of a large amount of aldosterone into the renal artery of isolated perfused hog kidney on the release of renin, prostaglandins (PG) and kinin and the excretion of urinary kallikrein were investigated. Infusion of aldosterone at a rate of 100 ng/min (100 to 800 ng/ml of perfusate) resulted in significant releases of renin, PG (PGE2 , 6-0-PGF1 alpha), and kinin and increase in urinary kallikrein. Infusion of aldosterone and an inhibitor of kallikrein, aprotinin, decreased the releases of renin, PG and kinin and infusion of aldosterone with indomethacin decreased the release of PG but increased that of kinin and urinary kallikrein without significant change in renin releases. These findings suggest that the release of renin by aldosterone may result from synergic effects of renal PG and the kallikrein -kinin system.

Aldosterone↗