Acute coadministrations of an inhibitor of
endopeptidase 24.11 (
thiorphan) and a
ligand (SC-46542) selective for the non-
guanylate cyclase-linked
atriopeptin binding sites increases urinary
sodium excretion to a greater degree in conscious spontaneously hypertensive rats than in normotensive Wistar-Kyoto rats. In the present study, we examined the effects of chronic 10-day
intravenous infusions of
SC-46542 (des[Phe106,Gly107,Ala115,Gln116]
atriopeptin-(103-126] (0.1 mg/kg/hr),
thiorphan (1.5 mg/kg/hr), and
atriopeptin-(103-126) (100 ng/hr) alone or in combination on direct recording of mean arterial pressure in conscious spontaneously hypertensive rats. During an 11-day time-control infusion of isotonic saline vehicle (100 microliters/hr), mean arterial pressure remained stable. Chronic infusion of
atriopeptin-(103-126) decreased mean arterial pressure progressively over the first 3 days; then mean arterial pressure progressively rose to control level over the following 3 days and remained at control level for the remainder of the experiment. Similarly, coinfusions of
atriopeptin-(103-126) and
SC-46542 or
thiorphan,
SC-46542 and
thiorphan, or the triple infusion of
atriopeptin-(103-126),
SC-46542, and
thiorphan had only transient effects on mean arterial pressure during 10-day infusions.
SC-46542 alone had no effect on mean arterial pressure. Similarly,
thiorphan alone had no effect on mean arterial pressure except at doses that blocked the acute pressor response to
angiotensin I. Chronic infusions of
atriopeptin-(103-126),
SC-46542, and
thiorphan alone or in combination are not effective long-term treatments for
hypertension in spontaneously hypertensive rats.