Mechanism of the antihypertensive effects of diuretics. Possible role of salt in hypertension.

The mechanism of the antihypertensive effect of chlorothiazide does not difler from that of such potent salt-depleting therapeutic agents as the mercurial diuretics and tlw rice diet. The extracellular fluid and plasma volumes are reduced and, as 44 result, right hecrrt filling pressure, cardiac output, and blood pressure (if abnormally elevated by some pressor stimu1u.y) fall. Becal4se of the reduction in plasma volume, drugs which increase the capacity of the peripheral vasculature, such as ganglioplegic agents, syncrgizc with chlorothiazide. The reasons for some of the contradictory interpret&ions of chlorothiazide activity are discussed and appear to be dt4e primarily to (I) the dificulty in assessing antihypertensive mechanisms in long-term studies and (2) conff4sion over the signijicunce of “normul” vukces for total exchangeable sodizcm in chronic experiments u>ith chlorothiazide. For the reasons stated, it is suggested that suit plays a permissive rather than. 14 primary etiological role in the genesis of essential hyptertension.