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Biomedical subjects

H Yoshimi

Publications and source records attributed to H Yoshimi.

At least 73 records · Page 4Linked to original sources

Effects of steroid and thyroid hormones on synthesis of atrial natriuretic peptide by cultured atrial myocytes of rat.

The in vitro effects of various steroid and thyroid hormones on synthesis of rat atrial natriuretic peptide (rANP) were studied using new-born rat atrial myocytes in culture. Dexamethasone, testosterone and triiodothyronine markedly stimulated both synthesis and secretion of immunoreactive (IR)-rANP with the same peak after 4-day-culture. Dexamethasone and testosterone dose-dependently (10(-7)-10(-6) M) stimulated synthesis of IR-rANP and were the most potent among various steroids tested. Triiodothyronine (T3) also stimulated synthesis of IR-rANP in a dose-dependent manner (10(-8)-10(-7) M), of which effect was more potent than that of tetraiodothyronine, whereas reverse T3 was ineffective. The present study clearly shows that glucocorticoids, androgens and thyroid hormones directly stimulate synthesis of ANP by atrial myocytes and suggests that ANP may play a potential role in mediating and/or modulating the biological effects by these hormones in the cardiovascular system.

Adrenal Cortex Hormones↗

Renal function curve in patients with secondary forms of hypertension.

The causative mechanisms of hypertension were investigated by studying the renal function (pressure-natriuresis) curve in patients with primary aldosteronism (n = 6) and renovascular hypertension (n = 6). Before and after radical operation (removal of adenoma in primary aldosteronism and percutaneous transluminal angioplasty in renovascular hypertension), dietary NaCl intake was altered from 10 to 13 g/day in Week 1 to 1 to 3 g/day in Week 2. Mean arterial pressure (MAP) and urinary sodium excretion were measured on the last 3 days of each week. By restricting sodium intake before operation, MAP was reduced from 122 +/- 7 to 113 +/- 7 mm Hg (p less than 0.025) in primary aldosteronism but not in renovascular hypertension (130 +/- 6 to 128 +/- 5 mm Hg). The renal function curve was drawn by plotting urinary sodium excretion on the ordinate and MAP on the abscissa before and after operation. The slope of the curve was analyzed between the plotted points, and each curve was extrapolated to zero sodium excretion as an estimate of the degree of shift of the curve along the MAP axis. Before, as compared with after operation, the extrapolated x-intercept of the curve was shifted rightward in both primary aldosteronism (111 +/- 7 vs 87 +/- 4 mm Hg; p less than 0.025) and renovascular hypertension (128 +/- 5 vs 95 +/- 2 mm Hg; p less than 0.025) and the slope was depressed in primary aldosteronism (16 +/- 1 vs 40 +/- 17 [mEq/day]/mm Hg; p less than 0.025) but not in renovascular hypertension (130 +/- 75 vs 40 +/- 13 [mEq/day]/mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regulation of plasma atrial natriuretic peptide and the cardiopulmonary baroreflex in the rat.

To study the physiological regulation of atrial natriuretic peptide (ANP), we examined the effects of volume expansion and depletion and the influence of cardiopulmonary baroreflex on plasma ANP levels in pentobarbital-anesthetized male Wistar rats. The volume expansion by acute intravenous saline infusion (2% of body weight) increased central venous pressure (CVP) and decreased heart rate (HR) in rats with intact baroreflex. The plasma ANP level in the volume expanded group was significantly higher than that in the control rats (453 +/- 100 vs 170 +/- 40 pg/ml, p less than 0.01). Conversely the plasma ANP level decreased from 214 +/- 15 to 125 +/- 13 pg/ml (p less than 0.01) accompanied by a fall in CVP and an increase in HR after nonhypotensive hemorrhage (0.8% of body weight). Hypotensive hemorrhage (2% of body weight) caused a progressive decrease in CVP while plasma ANP did not decrease further (141 +/- 25 pg/ml). Bilateral vagotomy did not modify either the basal plasma ANP level or the plasma ANP responses to volume expansion and depletion, though it inhibited HR response. These results indicate that in the rat, plasma ANP responds not only to volume expansion but also to moderate volume depletion suggesting that ANP may have a physiological role in body fluid homeostasis. The ANP response to changes in blood volume appears to be independent of the cardiopulmonary baroreflex with vagal afferent.

Animals↗

Effects of changes in dietary sodium intake and saline infusion on plasma atrial natriuretic peptide in hypertensive patients.

Plasma concentrations of immunoreactive (IR)-atrial natriuretic polypeptide (hANP) were measured by radioimmunoassay in 9 essential hypertensive patients after alteration of salt intake and acute saline infusion. Daily salt intake was altered every one week in the order of 15g/day, 3g/day, and 7g/day. On the last day of the first week, 1500 ml of 0.9% saline was infused intravenously over one hour. Plasma concentrations of IR-hANP tended to decrease, although not significant, by salt restriction. Further, there were significant positive correlations between changes in plasma concentrations of IR-hANP and those of several variables such as body weight, systolic blood pressure, and creatinine clearance. Plasma concentrations of IR-hANP rose significantly (p less than 0.05) from 50.7 +/- 20.1 (Mean +/- SEM) pg/ml to 119.0 +/- 48.8 after acute saline infusion. Although there was significant correlation between mean blood pressure and the increase in sodium excretion by saline infusion, this increase was unrelated to the rise in plasma concentrations of IR-hANP. These results suggest that the release of ANP is stimulated mainly by expansion of extracellular fluid volume in hypertensive patients. However, natriuretic and hypotensive effects attributable to the changes of ANP release could not be elucidated.

Adult↗

Hypertensive complications and home blood pressure: comparison with blood pressure measured in the doctor's office.

We have compared hypertensive target organ damage with home blood pressure readings (HBPs) and with office blood pressure readings (OBPs) in 100 patients with mild to moderate essential hypertension. The correlation between blood pressure levels and hypertensive target organ damage in HBPs and OBPs were similar (r = .42, p less than 0.001 for systolic HBPs; r = .33, p less than 0.001 for diastolic HBPs; r = .42, p less than 0.001 for systolic OBPs; r = .34, p less than 0.001 for diastolic OBPs). In most instances, HBPs were lower than corresponding OBPs. Among individual patients whose OBPs were identical, HBPs in some instances differed strikingly. Optic fundi abnormalities were significantly more severe in patients whose systolic HBPs were 150 mmHg or greater, than in those whose systolic HBPs were less than 150 mmHg (p less than 0.05). Hypertensive complications did not differ among office hypertensive patients who were normotensive or borderline hypertensive at home, from the differences of OBPs. We concluded that overall hypertensive complications were equally related to HBPs and OBPs, but patients with discrepancies between HBPs and OBPs had fewer hypertensive complications. Thus, both OBPs and HBPs should be considered in deciding therapy.

Adult↗

Vascular receptor binding activities and cyclic GMP responses by synthetic human and rat atrial natriuretic peptides (ANP) and receptor down-regulation by ANP.

Biological activities of a variety of synthetic human (h) and rat (r) atrial natriuretic peptide (ANP) and related peptides as assessed by receptor binding and cyclic GMP response, and regulation of vascular ANP receptors were studied in rat aortic vascular smooth muscle cells (VSMC) in culture. alpha-hANP1-28 and alpha-hANP7-28 equally inhibited the binding of 125I-labeled-alpha-hANP to its vascular receptors, whereas Met(O)12-alpha-hANP1-28 was less potent and reduced and carboxymethylated (RCM)-alpha-hANP1-28 was ineffective. rANP5-27 and rANP5-28 were equipotent in receptor binding, whereas rANP5-25 had somewhat less potent effect and rANP8-28 fragment was ineffective. alpha-hANP1-28, alpha-hANP7-28, rANP5-27 and rANP5-28 similarly stimulated intracellular cyclic GMP formation, whereas rANP5-25 showed less stimulatory effect, and RCM-alpha-hANP1-28, Met12-sulfoxide and rANP fragment were ineffective. Pretreatment with unlabeled alpha-hANP (3.2 X 10(-9) and 3.2 X 10(-8)M) for 24 hrs resulted in a substantial reduction (55 and 75%) of total receptor number without changing the affinity of ANP receptors. These results suggest that the common ring structure formed by the disulfide bond in the molecule is critical for receptor binding and subsequent biological actions, and that a hydrophobic amino acid located at the position of 12, and (24-26) residues at the C-terminal side, but not (1-6) at the N-terminal side, of the disulfide bridge may play a part in modulating receptor binding and/or biological functions. The present study also indicates "down-regulation" of vascular ANP receptors by homologous ligand.

1-Methyl-3-isobutylxanthine↗

Effect of synthetic human atrial natriuretic peptide on aldosterone secretion by dispersed aldosterone-producing adenoma cells in vitro.

The effect of synthetic alpha-human atrial natriuretic peptide (alpha hANP), a potent natriuretic and vasorelaxant polypeptide recently isolated from human atria, on aldosterone secretion was studied in vitro in collagenase-dispersed adrenal adenoma cells from a patient with primary aldosteronism. alpha hANP (3.2 X 10(-7) M) significantly inhibited both basal and potassium (16 mM)-stimulated aldosterone secretion, whereas it had little or no effect on aldosterone secretion submaximally or maximally stimulated by ACTH (3.4 X 10(-10)-3.4 X 10(-9) M) or angiotensin II (10(-8)-10(-9) M). The less potent effect of alpha hANP on aldosterone secretion by dispersed human adrenal tumor cells compared to that in in vitro animal studies may reflect decreased affinity and/or number of specific receptors for ANP on the tumor cells. Whether ANP plays a physiological role in regulation of aldosterone secretion in humans in vivo remains to be determined.

Adenoma↗

Specific receptors for atrial natriuretic factor (ANF) in cultured vascular smooth muscle cells of rat aorta.

Specific binding site for atrial natriuretic factor (ANF), a potent natriuretic and vasorelaxant polypeptide recently isolated from mammalian atria, was studied in cultured vascular smooth muscle cells (VSMC) of the rat aorta. Binding studies of 125I-labeled-synthetic alpha-human natriuretic peptide (alpha-hANP) revealed the presence of a non-interacting, single class of high affinity binding sites for alpha-hANP on VSMC in culture: the apparent dissociation constant (Kd) was approximately 1-2 X 10(-9)M and the number of maximal binding sites was approximately 200,000-300,000 sites/cell. A variety of vasoactive substances and other polypeptide hormones did not affect the binding of 125I-labeled-alpha-hANP to its binding sites. alpha-hANP significantly increased the concentrations of intracellular cyclic GMP in VSMC in a dose-dependent manner (3.2 X 10(-9)-1.6 X 10(-7)M). These data indicate that the specific receptor for ANF is present in VSMC and suggest that intracellular cyclic GMP may be involved in its vasorelaxant effect.

Animals↗