The antihypertensive effect of oral administration of pig pancreatic kallikrein was investigated in a double blind study of 20 patients with essential hypertension. Kallikrein treatment lowered the blood pressure (BP) significantly from 159.5/104.5 to 146J/92.8 mm Hg in the supine and from 153/106.1 to 136.1/95.6 mm Hg in the standing position. Blood pressure remained unchanged in the placebo group. Urinary kallikrein, sodium excretion, and GFR increased with treatment, but these changes did not reach statistical significance. In the kallikrein-treated patients but not in the placebo group, urinary kallikrein was correlated both to GFR (r = 0.7, p < 0.001) and sodium excretion (r = 0.5, p < 0.01). The antihypertensive mechanism of kallikrein treatment remains unknown. It could be speculated that kallikrein may induce changes in local blood flow, mediated by kinin and prostaglandin release. (Hypertension 3 (supp I): 1-18-1-21, 1981)
KEY WORDS • urinary kallikrein excretion • essential hypertension • kallikrein treatment
In this multicenter, double-blind study, the antihypertensive efficacy and safety of irbesartan were compared with those of atenolol in patients with mild-to-moderate hypertension. Following a 4- to 5-week placebo lead-in period, 231 patients with seated diastolic blood pressure (SeDBP) 95-110 mmHg were randomized to irbesartan 75 mg or atenolol 50 mg once daily for 24 weeks. Doses were doubled at Week 6 for SeDBP > or = 90 mmHg. At Week 12, or anytime thereafter, doses were doubled for SeDBP > or = 90 mmHg if not done at Week 6, and hydrochlorothiazide and then nifedipine were added. Efficacy was determined by change from baseline in blood pressure and by therapeutic response rates. Safety was assessed by monitoring adverse events (AEs). Both treatments significantly lowered blood pressure from baseline. There were no significant differences between treatment groups with respect to blood pressure changes or therapeutic response. Atenolol significantly reduced seated heart rate compared with irbesartan at Week 12. The incidences of serious AEs and discontinuations due to AEs were approximately twice as high in the atenolol group compared with the irbesartan group. Thus, in comparison to atenolol, irbesartan < or = 150 mg provided at least equivalent blood pressure control while demonstrating an excellent safety and tolerability profile.
Urinary kallikrein excretion was significantly lower in patients with essential hypertension (0.48 +/- 0.05 EU/24 h) than in normotensive controls (1.26 +/- 0.14 EU/24 h). Oral administration of hog pancreatic kallikrein normalized decreased urinary kallikrein and reduced arterial pressure. The treatment-induced rise in urinary kallikrein was due to an enhanced release of endogenous enzyme, as was determined by radioimmunoassay. It is proposed that in the hypertensive patients the low urinary kallikrein excretion reflects a defect in renal kallikrein formation which is normalized by oral kallikrein. The hypotensive action of oral kallikrein as well as its stimulating effects on renal kallikrein release suggest that the kallikrein-kinin system is involved in blood pressure regulation and that impaired renal kallikrein activity may be a factor in the maintenance of essential hypertension.
A study was conducted on 25 patients (18 men, seven women; mean age 48 [24-70] years) with essential hypertension (EH) to see whether an increase in potassium supply influences blood pressure as well as metabolic and hormonal parameters, and whether the anion administered together with potassium affects the results. In a randomized, cross-over trial sequence the patients daily received 120 mmol potassium chloride, 120 mmol potassium citrate or a placebo, each for 8 weeks. Between each of the three periods there was a "wash-out" phase of 4 weeks each. After 8 weeks of potassium citrate intake the systolic and diastolic pressures were reduced significantly, by a mean of 6.2/3.8 mm Hg (P < 0.05). But after potassium chloride there was only a small, not significant, reduction. Metabolic and hormonal parameters (fasting glucose concentration, glucose tolerance test, lipid electrophoresis; plasma renin activity, plasma concentration of aldosterone, noradrenaline and insulin) were not significantly changed.--These findings suggest that an increased supply of potassium has a favourable haemodynamic effect, but this varies markedly between different potassium salts. An increase in potassium supply should thus be considered as an additional measure in the treatment of EH. As long as renal function is normal no unfavourable metabolic effect need be feared.
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