Seasonal dosage-dependent hypersensitivity to the angiotensin II receptor blocker, losartan. A case report and review

Since it has been in clinical use for two decades, individual data permitting evaluation of the long-term treatment of hypertension with losartan, which blocks the dominant angiotensin-II receptor (AT ₁ R), should now be available. In the present case, by dosage adjustment according to daily home blood pressure (BP) readings, a mild degree of hypertension discovered during routine examination was kept in the 130/80 (mm Hg) range over an 11 year period (2003-2013). In the early years, control was achieved with 12.5 – 25.0 mg/day and dosage adjustment was seldom needed on a seasonal basis. However, on increasing to 50 mg/day, a profound downward adjustment to 0 – 12.5 mg/day was required in hot weather. The adjustment may have prevented recurrence of drug-induced postural hypotension and renal colic. Whether the adjustment facilitated an increased nocturnal BP, as suggested by some ambulatory BP studies, was not examined. A working hypothesis, consistent with animal experiments, is that under conditions of heat-stress (e.g. vascular dilation, salt loss), there is increased expression of a countervailing, losartan-insensitive, receptor subtype (AT ₂ R). By lowering BP in response to angiotensin-II, AT ₂ R would facilitate fine-tuningof the AT ₁ R-mediated vasoconstriction that supports BP when superficial veins dilate to enhance body cooling. This AT ₂ R activity might be sufficient to explain a small summertime BP dip found in normal human subjects whose Ang II levels are not increased. The dip would be greatly enhanced when Ang II levels were increased at higher losartan dosages. Close monitoring of losartan dosage may be necessary for those living in, or travelling to, geographical regions where temperatures are seasonally or continually high, and for those engaging in activities that involve such exposure (e.g. hot yoga, Turkish baths).