The ionic mechanism underlying the chronotropic effect of epinephrine on the rabbit sinoatrial (S-A) node has been studied. Epinephrine (5.5 X 10(-6) M) increased the spontaneous rate from 206 +/- 25 min-1 to 242 +/- 39 min-1. The effect of epinephrine was reproducible on repetitive applications. Voltage clamp experiments using the two microelectrode technique revealed the following changes in the membrane current: epinephrine (5.5 X 10(-7) M) increased the limiting conductance for the slow inward current (is) by approximately 30% and the potassium current (ik) by about 10%, keeping the kinetics of is and ik constant. From the holding potential of -70 mV the activation of is was observed on step depolarization positive to -60 or -55 mV in both control and epinephrine solution. The hyperpolarization-activated current (ih) was also increased by about 20% at -70 mV, and its time course was slightly accelerated. Participation of is for the chronotropic effect of epinephrine was strongly suggested by the findings that is was partially available positive to -60 mV and that epinephrine could not increase the slope of diastolic depolarization when is was blocked by D 600.

We measured serum urate in 3,258 Japanese outpatients. Five of them had persistent hypouricemia. Three also had microhematuria. Four of the five patients were proven to have renal uricosuria with hypouricemia, but otherwise normal tubular function. When tested with both pyrazinamide and benzbromarone, 1 patient had a presecretory reabsorption defect, 2 had postabsorption defects, and 1 an enhanced renal tubular secretion of urate. These results suggest that persistent hypouricemia in outpatients is of very low incidence, is usually caused by an isolated metabolic error of urate transport, and is not related to drug ingestion or systemic disease.

Hypertension is a common complication in patients with gout and/or hyperuricemia. Besides, hyperuricemia is a risk factor of gout as well as ischemic heart disease in hypertensive patients. Moreover, the risk of gout is modified by antihypertensive drugs. However, it remains unclear how antihypertensive agents affect uric acid metabolism. In the present study, we investigated the uric acid metabolism in treated hypertensive patients to find out whether any of them would influence serum levels of uric acid. 751 hypertensive patients (313 men and 438 women) under antihypertensive treatment were selected. Blood pressure (BP), serum uric acid (SUA) and serum creatinine (Scr) were measured and evaluated statistically. In patients treated with diuretics, beta-blockers and/or alpha-1 blockers SUA levels were significantly higher than in patients who were not taking these drugs. Besides, the estimated glomerular filtration rate (eGFR) in patients treated with diuretics, beta-blockers and/or alpha-1 blockers was negatively correlated with SUA level. There were gender differences in the effects of beta-blockers and alpha-1 blockers. Multiple regression analysis indicated that both diuretics and beta-blockers significantly contributed to hyperuricemia in patients with medication for hypertension. Diuretics, beta-blockers and alpha-1 blockers reduced glomerular filtration rate and raised SUA levels. Calcium channel blockers, ACE inhibitors and angiotensin receptor blockers, including losartan, did not increase SUA levels.

No abstract

To investigate the relation between basal coronary artery diameter and development of coronary artery spasm, the diameters of the proximal, middle and distal segments of the three major coronary artery branches, together with that of the left main trunk, were measured on a control angiogram and after ergonovine and nitrate administration in 30 patients with vasospastic angina without significant organic stenosis, and in 35 patients without ischemic heart disease. The percent change in coronary diameter after ergonovine and nitrate administration compared with the control diameter was used as an index of coronary vasoreactivity. In patients with vasospastic angina, coronary artery responses to both ergonovine and nitrate were greater in the spastic segments than in the other segments (p less than 0.05), and those of the coronary arteries without spasm were greater than those of the coronary arteries in patients without ischemic heart disease (p less than 0.01). There were no significant differences between the coronary artery diameters in the two groups after nitrate administration, and the control diameters were less in patients with vasospastic angina than in patients without ischemic heart disease. These observations indicate that a coronary vasomotion disorder, which involves increased basal coronary artery tone and hypersensitivity to vasoconstrictive stimuli, not only at a localized segment but also in the entire coronary artery tree, is present in patients with vasospastic angina. Clinically, evaluation of basal coronary artery tone may be useful for predicting the occurrence and location of coronary artery spasm.

The changes in membrane resistance during the pacemaker current cannot be accounted for by K depletion and suggest that in the range of diastolic depolarisation the pacemaker current results predominantly from a time dependent decrease in K conductance.

Two patients with primary hyperparathyroidism had hyperuricemia due to the decrease in urate clearance. In analysis by 4-component model system, the tubular secretion of urate commonly decreased without changes in either filtered urate or presecretory reabsorption of urate. Both patients had a reduction of urea clearance, and both parathyroidectomy in the former case and intravenous infusion of saline in the latter case could reduce the serum urate level associated with the increase in the ratio of urate clearance to creatinine clearance. It is of interest that the former case with a higher serum urate level had a relatively higher postsecretory reabsorption, even with the decrease in tubular secretion of urate. However, the latter patient with a lower serum urate level had a decrease in postsecretory reabsorption of urate in pro portion to the decrease in tubular secretion. These results suggest that in hyperuricemia patients with primary hyperparathyroidism, the reduction of tubular urate secretion via hypoperfusion of the capillary network is typically present, however, the severity of the hyperuricemia might be dependent on the dysfunction of the postsecretory reabsorption of urate. (Internal Medicine 31: 807-811, 1992)

Allylic p-tolyl sulfones were easily desulfonylated to the corresponding alkenes by LiHBEt3 in the presence of a catalytic amount of [PdCl2(dppp)] under mild conditions with the preservation of the original stereochemistry. This reaction was successfully applied to the synthesis of squalene.