Rats susceptible to the hypertensive effect of dietary
salt (SS/Jr) have excess urinary
19-nordeoxycorticosterone compared with
salt-resistant control rats (SR/Jr).
19-Nordeoxycorticosterone is a hypertensinogenic
mineralocorticoid, but whether it contributes to the
salt sensitivity of SS/Jr is unknown. This study sought to evaluate the contribution of
19-nordeoxycorticosterone to the
salt sensitivity of SS/Jr by lowering its production with an
aromatase inhibitor, 10-propargyl-androst-4-ene,3,17-dione (19-acetylenic-androstenedione, 19-AA). This
aromatase inhibitor also preferentially inhibits nonaromatizing adrenal 19-hydroxylation, an essential step in the formation of
19-nordeoxycorticosterone. To test this hypothesis, inhibitor (120 mg) or vehicle pellets were implanted into male and female weanling SS/Jr at 42 days of age. A high
salt diet (8% NaCl) was started and two additional pellets were implanted at 52 and 62 days of age. Systolic blood pressure was measured in all animals and urinary
corticosteroids in males. Compared with vehicle, the inhibitor lowered blood pressure at 50 days of age (when it could first be measured) until 64 days of age in females and 71 days of age in males.
Corticosterone and
aldosterone levels were not different between 19-AA- and vehicle-treated SS/Jr.
19-Nordeoxycorticosterone levels, however, were mildly reduced with the inhibitor (0.05 less than p less than 0.10). After 28 days of high
salt diet all 23 of the 19-AA-treated SS/Jr were alive, whereas almost one half of the control animals had died. These data demonstrate that 19-AA attenuates the
hypertension in SS/Jr; this effect may be through reduction in
19-nordeoxycorticosterone production.(ABSTRACT TRUNCATED AT 250 WORDS)