Acute effect of furosemide on renal kallikrein and prostaglandin systems in mild to moderate essential hypertension.

The activity of basal 24-hour urinary kallikrein activity (UKA), prostaglandin E2 (U. PGE2) and thromboxane B2 (U. TxB2) and their relationship to natriuresis (U. Sodium), urinary aldosterone (U. Aldosterone) and plasma renin activity (in supine position: PRA1; in standing position: PRA2) were evaluated in 20 patients with early-moderate hemodynamically defined (first pass and gate blood pool radionuclide angiocardiography) essential hypertension (H) and in 13 age-matched normotensive patients (N). In basal conditions, UKA and PRA2 were significantly reduced (p less than 0.005 and p less than 0.05, respectively) in H compared with N. However, no differences between N and H were found for U. TxB2, U. PGE2, U. Aldosterone, U. Sodium, and PRA1. All parameters were also evaluated both in H and N before and after the administration of furosemide (40 mg i.v.). In H, but not in N, furosemide induced an increase of UKA (p less than 0.05), U. TxB2 (p less than 0.05) and U. Sodium (p less than 0.001). In both H and N furosemide caused a significant rise of PRA1 (p less than 0.001 in H and p less than 0.01 in N) and PRA2 (p less than 0.001 in H and p less than 0.05 in N). In H a significant correlation was found between percent increases of U. Sodium and U. Kallikrein (r = 0.54, p less than 0.01) and between percent differences of PGE2 and TxB2 (r = 0.59, p less than 0.01). It is proposed that reduction of basal UKA may be an early evidence of the first stages of hypertension, i.e., in absence of renal and cardiovascular alteration. The finding is not accompanied by significant changes in urinary excretion of arachidonic acid metabolites and aldosterone. Finally, any relation between UKA values and systemic hemodynamics is lacking.

Hemodynamics in borderline hypertension: acute effect of furosemide.

In order to identify the hemodynamics of borderline essential hypertension, radionuclide angiography was performed before and after bolus injection of furosemide (40 mg i.v.) both at 3 min (i.e. before diuretic effect) and at 30 min (i.e. after diuretic effect) in 16 borderline (B) patients and in 14 age-matched WHO classification I-II essential hypertensives (H) patients. 14 age-matched normotensive (N) subjects were used as controls. B patients were further subdivided into two subgroups according to a cardiac index under or above 3 liter/min/m2 in basal conditions. Baseline hemodynamic characteristics showed higher values of mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) in both H and B patients when compared with N subjects (p less than 0.001). Furthermore, B and H patients exhibited lower values of left ventricular peak filling rate (PFR) than seen in N subjects (p less than 0.01 and p less than 0.05, respectively). H patients demonstrated higher peak systolic blood pressure/endsystolic volume ratio (PSP/ESV) than seen in N subjects (p less than 0.05). PFR positively correlated with peak emptying rate (PER) only in N and B patients (p less than 0.05). After furosemide administration, even though differences were observed in the absolute values, B and H patients showed similar hemodynamic patterns. Only the B subgroup with cardiac index (CI) greater than 3 liter ('volume-dependent' patients) showed a decrease in left ventricular end-diastolic volume index (LVEDVI) at 30 min associated with a lowering of stroke index (SI; p less than 0.005 for both), when compared with pre-drug values. In B patients with CI less than 3 liter ('afterload-dependent' patients) no differences were observed either at 3 min or at 30 min in comparison with values obtained prior to drug administration. Moreover, in this subgroup, like in H patients, there was a negative correlation (p less than 0.01) between 3-min percent change of SVRI and 3-min percent change of SI. Our data suggest that in 'borderline' hypertension: (a) there may be an increase in peripheral resistance, as in established hypertension, especially when age-matched groups are considered; (b) the earliest sign of compromised left ventricular function is the reduction in diastolic PFR but, unlike established hypertension, this index is still correlated with systolic function; (c) cardiac output might be even somewhat reduced and also negatively correlated with vascular resistance ('afterload-dependent' hearts); (d) furosemide (acute administration) might contribute to a better definition of hemodynamic behavior.

Effects of calcitonin on limb blood vessels in human obstructive arterial disease.

To check the possibility of a vasoactive effect of calcitonin in man, the authors treated ten hospitalized patients (seven males and three females, mean age 66.3 +/- 3.24), suffering from obstructive arterial disease in the lower extremities, with 100 units M.R.C. i.m. daily, for a period of 15 days. Five patients presented Raynaud's phenomenon. Treatment (B) led to an improvement of subjective symptomatology and to the disappearance of Raynaud's phenomenon in comparison with symptoms before treatment (A) and after a placebo period of 15 days (C). With respect to instrumental parameters, calcitonin induced: a) a slight increase of segmental plethysmography values (height/width ratio of curves) if compared with A (p less than 0.05) and more significantly if compared with C (p less than 0.01 and less than 0.0125, from right and left sides, respectively); b) a small change in venous-occlusion plethysmography values, if compared with A and C, both in basal conditions and after the "ischaemic test"; c) a significantly lesser reduction of digital photoelectric plethysmography values (height/width ratio of curves) after the "cold test" in comparison with A (p less than 0.01, both on the second and on the third fingers of the right hand), as well as with C (p less than 0.01 and p less than 0.025, on the second and on the third fingers, respectively). The present investigation points out the vasoactive influence of calcitonin in human obstructive disease. Results show the improvement in collateral limb circulation and, above all, in the amount of cutaneous flow. Little information is available on the mechanism of this effect, for which only hypotheses can at present be advanced.