The effects of Ro 12-4713, a vasodilator, on blood pressure and heart rate, were tested in 13 ambulant patients with mild to severe hypertension. The patients received Ro 12-4713 in total oral doses ranging from 1.5 to 4 mg/kg over a 3-5 day period. Standard laboratory tests were done 24 h before and after the study. Standing and supine blood pressure and heart rate were determined before, and every hour for 6-8 h after drug administration. ECGs were recorded before, during and at the end of each study day. Ro 12-4713 reduced the pretreatment standing and supine-blood pressure from 213 +/- 34/126 +/- 21 mmHg and 218 +/- 31/130 +/- 20 mmHg to 156 +/- 33/85 +/- 9 mmHg and 158 +/- 25/88 +/- 11 mmHg at the end of Day 5. Heart rate was only transiently increased in patients with pretreatment values of less than 90 beats/min. Although abnormal ECGs tended towards normalization, there were 2 cases of T-wave inversion (the patients remained asymptomatic). Raised BUN levels tended to decrease towards normal. Side effects reported spontaneously by patients (headaches, palpitations, dizziness, nausea and one case of water retention) appeared to be transient in nature. Ro 12-4713 appeared to be a very potent and long lasting antihypertensive agent, whose inherent side effects were only transient in nature.

ABSTRACT— Following intravenous administration of 500 mg/kg b.wt. galactose, Galactose Elimination Capacity (GEC, mg/min/kg) was determined in 24 subjects with chronic non‐cirrhotic liver disease (CLD), 33 with liver cirrhosis and 11 controls. GEC was significantly (P<0.01) reduced in both CLD and cirrhosis. A statistically significant difference (P<0.01) was present between these two groups. Following the plasma disappearance curve at concentrations below 1.25 mmol/1, at which the extraction coefficient is assumed to be equal to one, the “Efficient Hepatic Blood Flow” (EHBF, ml/min) was determined in 11 consecutive cirrhosis patients, seven patients with CLD and 11 controls. EHBF was normal or slightly reduced in CLD as compared to controls (1046 ± 216 vs. 1471 ± 156 ml/min, mean ± SEM, n.s.) whereas it was markedly reduced in cirrhosis (846 ± 96 ml/min, mean ± SEM, p<0.001). Interestingly, a significant linear correlation (r = 0.757, p<0.001) was present between EHBF and the plasma clearance of sulfobromophthalein. No correlation was present, on the other hand, between the value of GEC and that of EHBF. These data indicate that after a single intravenous injection of galactose, the hepatic blood flow passing through the enzymatically active parts of the liver (i.e. excluding shunts) can be measured.

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