Kiyonobu Tanaka

The effect of docarpamine, a dopamine pro-drug, on blood pressure and catecholamine levels in spontaneously hypertensive rats.

We studied the effects of bolus intravenous injection of the dopamine prodrug, docarpamine (200 μg/kg), on mean arterial pressure (MAP) and heart rate (HR) in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). In WKY rats (n=18), MAP and HR increased 5 min after docarpamine and then returned to baseline levels within 15 min. In contrast, in SHRs (n=15), MAP and HR gradually decreased, reaching a nadir 20 min after injection. Five min after docarpamine, plasma dopamine and 3,4-dihydroxy phenyl acetic (DOPAC) levels increased in both WKY rats (n=5) and SHRs (n=5). The docarpamine-induced changes in MAP and HR in both rat strains (n=5/strain) were blocked by the D1-like antagonist, SCH23390. α-Adrenergic (n=4) and vasopressin V1 (n=3) receptor blockade also abrogated the effects of docarpamine in WKY rats. We conclude that docarpamine differentially affects MAP and HR in WKY and SHRs. In SHRs, the depressor and bradycardiac effects of docarpamine are mediated by D1-like receptors. In WKY rats, the pressor and tachycardiac responses are caused by an interaction among D1-like, α-adrenergic, and V1 receptors.

[Hepatopulmonary syndrome: clinical report of two cases].

症例1は57歳,女性.労作時呼吸困難を主訴に受診. PaO250.6Torrと低酸素血症を認めた.症例2は68歳,女性.肝細胞癌の治療目的にて入院中に労作時息切れが出現. PaO255.3Torrと低酸素血症を認めた.両症例とも基礎疾患として肝硬変症を認めること,ガス交換異常を伴う低酸素血症を認めること,マルチスライスCT (MSCT)にて肺内末梢血管拡張を認めることから肝肺症候群と診断した.

[Altered responses of heart rate, renal sodium handling and plasma growth hormone to clonidine in type II diabetic patients].

The aim of the present study is to explore whether the renal and cardiovascular response to clonidine in type II diabetic patients is different from that in control subjects, and to clarify the role of central alpha 2-receptor in the regulation of cardiovascular response and sodium handling in type II diabetes mellitus (DM). Thirty-five diabetic inpatients aged 30-71 years (54.1 +/- 9.7) and ten control subjects (N) were enrolled in this study after their fasting plasma glucose had been improved. To evaluate the peripheral sympathetic nerve activity, 24-hour urinary catecholamine was measured, and pulse rate (PR) responses to a 30-second standing test was determined. On another day, blood pressure (BP), PR, plasma norepinephrine (PNE), cyclic AMP (p-cAMP), renin activity (PRA), aldosterone (PAC) and growth hormone (p-GH) were measured at 0, 30, 60, 90, 120, 150, 180 minutes following the oral administration of clonidine (150 micrograms). Type II DM were classified as DM with hyper-response (DM-HR, n = 12) when their PR decreased after clonidine more than that of N, and if not, they were classified as DM with normal response (DM-NR, n = 23). Urinary catecholamine excretions in type II DM were within the normal range. BP, PNE and p-cAMP were markedly decreased with clonidine in similar fashion in DM-NR, DM-HR and N. The percent changes of PNE were correlated positively with the changes of p-cAMP in both N and DM-NR (r = 0.660 and 0.449, respectively), but not in DM-HR. No significant difference in the changes of p-GH (delta p-GH) and integral of GH (the area under the curve) following clonidine administration was observed in the three groups. The decrease in PR was correlated with neither delta p-GH (N: r = 0.082, DM-NR: r = -0.400, DM-HR: r = 0.242) or integral of GH (N: r = 0.191, DM-NR: r = 0.382, DM-HR: r = 0.162). The fractional excretion of sodium (FENa) decreased in N (p < 0.01), increased in DM-NR (p < 0.05) and did not change in DM-HR. The changes of FENa were not correlated with those of PRA and PAC.(ABSTRACT TRUNCATED AT 400 WORDS)

The Significance of cGMP and Dopamine Receptor on the Natriuretic and Hypotensive Activities of Synthetic Atrial Natriuretic Polypeptide in Essential Hypertension

This study was undertaken to clarify the role of dopamine receptor (DA2) on the effects of atrial natriuretic polypeptide(ANP) on blood pressure, plasma and urinary cyclic GMP, and urinary sodium excretion, alpha-human ANP (alpha-hANP) was intravenously administrated to 7 normal subjects and 14 patients with essential hypertension as follows: first a dose of 0.01 micrograms/kg/min for 30 minutes, and then 0.03 micrograms/kg/min with or without metoclopramide(MC) for 30 minutes. After the infusion of the 0.03 micrograms/kg/min dose of alpha-hANP, systolic blood pressure fell from 115 +/- 17 mmHg to 109 +/- 15 mmHg in normal subjects, and fell significantly from 163 +/- 33 mmHg to 145 +/- 26 mmHg in patients with essential hypertension. Diastolic blood pressure fell from 101 +/- 14 mmHg to 92 +/- 7 mmHg in patients with essential hypertension but did not change in normal subjects. A dose of 0.03 micrograms/kg/min of alpha-hANP led to a threefold rise in urine volume and twofold rise in urinary sodium excretion in normal subjects, and a fivefold rise in urine volume and fourfold rise in urinary sodium excretion in patients with essential hypertension. However, there was no relationship between the hypotensive and natriuretic effects of alpha-hANP in either normal subjects or patients with essential hypertensions. The infusion of a 0.03 micrograms/kg/min dose of alpha-hANP increased plasma cyclic GMP concentration from 4.1 +/- 2.1 pmol/ml to 34.3 +/- 25.Opmol/ml in normal subjects and from 4.5 +/- 2.6 pmol/ml to 20.3 +/- 7.4 pmol/ml in patients with essential hypertension. The rise in plasma cyclic GMP by alpha-hANP was suppressed by MC both in normal subjects and patients with essential hypertension. Urinary cyclic GMP excretion also increased during the infusion of alpha-hANP, but this effect was not suppressed by MC. Furthermore, plasma aldosterone concentration (PAC), which was depressed by alpha-hANP in normal subjects and patients with essential hypertension, was increased by MC. These results suggest that the hypotensive effect of alpha-hANP may depend not only on the natriuretic effect, but also on vasodilatation, the inhibition of aldosterone production or the suppression of the sympathoadrenomedullary system. Cyclic GMP may be produced through the DA2 receptor in vascular tissue but not in the kidney.