Captopril, Aldosterone and Urinary Kallikrein in Primary Hypertension

Abstract

The effects on blood pressure, the renin-angiotensin-aldosterone and the kallikrein-kinin systems were investigated in 32 patients with primary hypertension WHO stage I-II treated with captopril. Hydrochlorothiazide was added if needed to achieve a supine diastolic blood pressure of less than or equal to 90 mmHg. A placebo control group (n=8) was treated similarly. Supine mean arterial pressure fell from 133 +/- 10 on placebo to 114 +/- 12 mmHg after 4 weeks on captopril. At the same time plasma aldosterone decreased from 263 +/- 188 to 164 +/- 101 pmol . 1(-1), 24 h urinary excretion of aldosterone from 18 +/- 12 to 12 +/- 10 nmol and kallikrein from 9.0 +/- 6.7 to 6.2 +/- 4.1 nkat. Plasma angiotensin II was significantly reduced after two weeks treatment from 23.2 +/- 8.6 to 17.0 +/- 6.7 pmol . 1(-1). Before, but not during captopril, 24 h urinary kallikrein excretion correlated with plasma aldosterone levels and 24 h urinary aldosterone excretion (r=0.44 p, less than 0.05 and r=0.53, p less than 0.01, respectively). Mean arterial pressure reduction on captopril correlated with pretreatment PRA (r=0.44, p less than 0.05) but not with other measured hormone levels or changes therein. The addition of hydrochlorothiazide caused a further fall in blood pressure, but increased plasma aldosterone and 24 h urinary kallikrein excretion. Hydrochlorothiazide alone increased only 24 h urinary aldosterone excretion significantly. These findings indicate that, besides aldosterone secretion and renal arterial pressure, further mechanisms regulating the release of and activity of the renal kallikrein-kinin system exist.

Changes in the Renin‐Angiotensin‐Aldosterone and Kallikrein‐Kinin Systems During Normal and Hypertensive Pregnancy

“…The activity of the kallikrein-kinin system has been evaluated by measuring urinary kallikrein excretion (tu-Kall). The method used has been described by Asmundsen et al (1) and validated by us previously (28).…”

Is population-wide diuretic use directly associated with the incidence of end-stage renal disease in the united states?

“…Independent animal and human trials have demonstrated that diuretic therapy stimulates growthpromoting, profibrotic or proinflammatory substances such as homocysteine [7], plasminogen-activator inhibitor (PAI-1) [8], platelet-derived growth-promoting activity [9], low-density lipoprotein (LDL)-cholesterol [10], aldosterone [11], endothelin [12], and angiotensin II levels [13], which in turn increase transforming growth factor β (TGF-β) levels, tumor necrosis factor-α, and nuclear factor-κB [14]. Diuretic treatment stimulates renal production of cyclooxygenase 2 (Cox-2) [15], which may also play a role in promoting renal fibrosis, because Cox-2 inhibition has been shown to retard the progression of renal injury in rats [16].…”

Hypertension in Pregnancy. Prostaglandins, Kinins and Kallikrein

“…This method uses a chromogenic synthetic substrate (S-2266) and has been validated in our laboratory (9). Coefficient of variation (inter-assay) is about 6%.…”