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Three patients with postural hypotension (two of the idiopathic type, one possibly due to familial dysautonomia) were found to have not only the pathognomonic postural hypotension, without rise in heart rate, cardiac output and peripheral vascular resistance, but also a similarly abnormal regulatory mechanism on ergometric stress when recumbent. There was a delayed-response to the bloodpressure fall on Valsalva a manoeuvre, and the blood volume was reduced. A combined effect of these factors explains that these patients have a more marked impairment of physical capcity than might be expected merely from the orthostatic hypotension. The actions of noradrenaline, adrenaline, phenylephrine, isoproterenol, angiotensin and tyramine on blood pressure and heart rate were different from normal. Plasma-renin activity was reduced in all three patients and could not be raised. Urinary excretion of adrenaline and noradrenaline was markedly diminished. Reactions to noradrenaline and tyramine, as well as the excretion pattern of the catecholamine metabolites suggest a disorder of active adrenaline liberation. Furthermore, different disorders of catecholamine metabolism underlie idiopathic orthostatic hypotension and familial autonomia. Therapeutic trials with fludrocortisone, beta-receptor blockers and levodopa brought improvement, but long-term results are not yet available.

The blocking effects of metacaine-methanesulfonate (MS-222; abbreviated MMS) and of the corresponding hydrochloride (MHC) on the ionic currents in potential clamped myelinated nerve fibres were investigated. The dose-response relationships of MMS for blocking the Na-currents and K-currents could be satisfactorily fitted to the Langmuir adsorption isotherm with KNa = 0.7 mmol/l and KK = 1.8 mmol/l. The observed loss of efficacy in blocking ionic currents of 3-day-old solutions containing MMS was assumed to be due to a partial decomposition of the drug. We separated the water-soluble decomposition products by extraction of the metacaine base. The remaining aqueous solution showed an anti-blocking effect on metacaine blocked Na-currents. From corresponding experiments on the blocking effect of MHC we conclude that the anti-blocking effect is due to yet unknown decomposition products, formed in MMS but not in MHC solutions.

The direct action of arginine-vasopressin (AVP) and its deamino-D-arginine analogue (DDAVP) on renin release (RR) has been studied in isolated rat kidneys perfused with an electrolyte solution at constant pressure in a single-pass system. AVP and DDAVP infused at various concentrations (80 to 2100 pg/ml and 80 to 8700 pg/ml, respectively) reduced volume and increased osmolality of urine in a dose-dependent way. High doses of AVP reduced renal perfusate flow and glomerular filtration rate while DDAVP had no effect on renal haemodynamics. When vasoconstrictor doses of AVP or high concentrations of DDAVP were infused, "basal" RR remained unchanged. However, when RR had been stimulated by infusion of isoproterenol, vasoconstrictor doses of AVP as well as high doses of DDAVP which did not increase renal vascular resistance diminished RR by about 30% (P less than 0.01, and P less than 0.05, respectively). These results suggest that the inhibition of RR by vasopressin is not related to its vasoconstrictor action.

The role of cyclic AMP in the regulation of renin release (RR) was studied in isolated rat kidneys, which were perfused at constant pressure in a single-pass system with a modified Krebs-henseleit solution. Isoproterenol (IP) (2 x 10(-9) to 2 x 10(-6) M) and 3-isobutyl-1-methyl-xanthine (IBMX) (4 x 10(-7) to 7 x 10(-5) M) induced a dose-dependent increase of renal perfusate flow, glomerular filtration rate and urinary sodium excretion. RR was stimulated up to 10-fold above control values within 5 min. At the lowest concentrations IP stimulated RR, but did not affect renal haemodynamics. When IP and IBMX were administered concomitantly, a supraadditive stimulation of RR was observed. Dibutyryl-cAMP (db-cAMP) and 8-Br-cGMP (10(-6) to 10(-4) M) produced a similar dose-dependent vasodilation and natriuresis, but differed in their action on RR. Within 15 min after the start of the infusion, db-cAMP increased RR up to 4-fold, whereas 8-Br-cGMP was without an effect. These results suggest that IP, IBMX and db-cAMP stimulated RR by increasing the concentrations of cAMP in the epitheloid cells and independently of changes in renal haemodynamics and sodium excretion.

The importance of diabetic angiopathy for prognosis and course of diabetes mellitus, possibilities and basis of angiological therapy Complications originating from the vascular system determine life expectancy of the diabetic patient. He is particularly endangered by apoplexy, heart attack, arteriosclerosis of the lower extremities, retino- and nephropathy. Microangiopathy is a specific diabetic problem, the development of which shows a clear dependency on the quality of metabolism. Conventional therapy of circulatory problems today is less concerned with the vascular system than with the qualities of blood viscosity. In this context, viscosity is of main concern. Particularly in microcirculation viscosity is dependent on blood factors such as: haematocrit, plasmaviscosity, erythrocytes and thrombocytes. Their changed behaviour results, in the case of diabetes mellitus, in an increase in viscosity partly dependent on metabolism. A promising concept of treatment is available by pharmaceutically influencing the alteration of erythrocytes.