This systematic review shows that hydrochlorothiazide has a dose-related blood pressure-lowering effect. The mean blood pressure-lowering effect over the dose range 6.25 mg, 12.5 mg, 25 mg and 50 mg/day is 4/2 mmHg, 6/3 mmHg, 8/3 mmHg and 11/5 mmHg, respectively. For other thiazide drugs, the lowest doses studied lowered blood pressure maximally and higher doses did not lower it more. Due to the greater effect on systolic than on diastolic blood pressure, thiazides lower pulse pressure by 4 mmHg to 6 mmHg. This exceeds the mean 3 mmHg pulse pressure reduction achieved by ACE inhibitors, ARBs and renin inhibitors, and the 2 mmHg pulse pressure reduction with non-selective beta-blockers as shown in other Cochrane reviews, which compared these antihypertensive drug classes with placebo and used similar inclusion/exclusion criteria.Thiazides did not increase withdrawals due to adverse effects in these short-term trials but there is a high risk of bias for that outcome. Thiazides reduced potassium, increased uric acid and increased total cholesterol and triglycerides.

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Ca2+extrusion from rabbit inferior vena cava smooth muscle was studied using ratiometric fura 2 fluorimetry. Concomitant blockade of the plasma membrane Ca2+-adenosinetriphosphatase (ATPase; PCMA), Na+-Ca2+exchanger, and sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) completely prevented the decline in intracellular Ca2+ concentration ([Ca2+]i) normally observed when Ca2+ is removed from the extracellular space (ECS) after stimulated Ca2+ influx. Blockade of the Na+-Ca2+exchanger by removal of external Na+ reduced the rate of [Ca2+]idecline by 47%. Blockade of SERCA with cyclopiazonic acid reduced it by 23%, and this was not additive to the effects of Na+ removal. Exposure to nominally Ca2+-free solution prevented the sarcoplasmic reticulum (SR) from reloading only if the Na+-Ca2+exchanger was operational. Our results can be explained by an SR contribution to Ca2+ extrusion in which SERCA is arranged in series with Na+-Ca2+exchange.

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