Renin-Angiotensin-Aldosterone System During Chronic Thiazide Therapy of Benign Hypertension

Abstract

Activity of the renin-angiotensin-aldosterone system was investigated in 53 patients with benign essential hypertension treated with thiazides. Following acute (less than 3 weeks) exposure to thiazide, renin activity was increased in peripheral plasma and sensitivity to infused angiotensin was decreased but only when dietary salt was simultaneously restricted. During chronic (more than 2 months) exposure to hydrochlorothiazide, 32 patients with unrestricted salt intake had normal renin activity in peripheral plasma (39 of 43 determinations), normal sensitivity to infused angiotensin (18 of 22 tests), and normal aldosterone excretion (nine of nine assays). Renin activity correlated well with angiotensin sensitivity (r =0.661; P < 0.001). Therefore, chronic ingestion of thiazide apparently induces no change in the renin-angiotensin-aldosterone system and hence presumably neither secondary aldosteronism nor negative sodium balance.

Effect of potassium-sparing diuretics on the renin-angiotensin-aldosterone system and potassium retention in heart failure.

“…Hormone levels were unremarkable before the addition of amiloride or spironolactone despite doses of frusemide up to 160 mg daily. Since previous studies (Espiner et al, 1969;Nicholls et al, 1974) have shown that hyperaldosteronism frequently occurs towards the end of the diuretic phase in oedematous patients receiving frusemide, it appears that 'adaptation' of the reninangiotensin system may occur with maintenance frusemide therapy, similar to that described in hypertensive patients receiving chronic diuretic therapy (Bourgoignie, Catanzaro, and Perry, 1968).…”

Effect of chronic diuretic treatment on the plasma renin‐angiotensin‐ aldosterone system in essential hypertension.

“…Treatment with hydrochlorothiazide and tienilic acid for 3 weeks caused a significant rise in PRA (Figure 2) and no substantial decline during prolonged treatment for 48 weeks was observed. However chronic hydrochlorothiazide therapy has been reported to increase renin less than acute administration (Bourgoignie et al, 1968). Similarly a comparative study of shows that the increase in PRA after 14 weeks of metolazone or hydrochlorothiazide treatment was less than after 1 week of diuretic treatment.…”

“…Compared to the run-in period PRA was significantly (P< 0.01) increased and no decline in PRA was seen during prolonged diuretic treatment for up to 48 weeks. Times (weeks) Figure 1 Changes (mea ± s.e.mean) in plasma renin activity (PRA) during the first 3 weeks of treatment with either a fixed dose of tienilic acid (upper panel) Gross, 1979;Huang et al, 1979;Bourgoignie et al, 1968;, with tienilic acid (Maxwell & Gross, 1979;Huang et al, 1979) or with metolazone (Dornfeld & Kane, 1977) while the degree of stimulation of PRA and the time of course of PRA changes differs from study to study. In the present study using a constant but rather small daily dose of tienilic acid (250 mg) we found a maximal increase in PRA after one week and a levellingoff during the second and third week (Figure 1).…”

“…Whether this hyperreninemia is sustained during chronic diuretic treatment remained however unsettled since some authors reported a persistent elevation (Laragh, 1973;Morganti et al, 1979;Van Brummelen, Man In 't Veld & Schalekamp, 1980) while others found only a transient one (Bourgoignie, Catanzaro & Perry, 1968;Maxwell & Gross, 1979).…”

Renin and beta‐adenoceptor blockade‐the mechanism of the hypotensive effect?

“…The suggestion that concurrent treatment with ,B-adrenoceptor blocking drugs and diuretics will allow suppression of thiazide-induced renin secretion (Stokes, Weber & Thornell, 1974) is probably irrelevant as Bourgoignie, Catanzaro & Perry (1968) have show that the raised plasma renin activity is not evident with long term thiazide therapy.…”