We examined the interaction of a non-
guanylate cyclase-linked
atriopeptin (AP) binding site
ligand,
SC-46542 (des[Phe106,Gly107,Ala115,Gln116]AP-(103-126], and an
endopeptidase 24.11 inhibitor,
thiorphan, on mean arterial pressure, urinary
sodium excretion, urinary cyclic
guanosine monophosphate (cGMP) excretion, plasma cGMP concentration, and plasma AP immunoreactivity (ir) in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Compared to vehicle control rats, coadministration of
SC-46542 and
thiorphan increased urinary
sodium excretion in SHR from 2.1 +/- 0.3 to 11.6 +/- 0.7 microEq/min/100 g
body weight and in WKY from 1.6 +/- 0.4 to 4.4 +/- 0.4 microEq/min/100 g
body weight, and increased urinary cGMP excretion in SHR from 2.7 +/- 0.5 to 79.0 +/- 17.5 pmol/min/100 g
body weight and in WKY from 7.0 +/- 3.0 to 72.4 +/- 10.6 pmol/min/100 g
body weight. The change in urinary
sodium excretion was greater in SHR than WKY. The coadministration of
SC-46542 and
thiorphan had greater effects on urinary
sodium excretion and urinary cGMP excretion than administration of either compound alone. Coadministration of
thiorphan and
SC-46542 had no effect on glomerular filtration rate or plasma cGMP concentration, suggesting that the urinary cGMP excretion response was nephrogenous. Compared to vehicle control rats, plasma APir was increased during coadministration of
SC-46542 and
thiorphan in both SHR (998 +/- 76 v 5.10 +/- 116 pg/mL) and WKY (775 +/- 36 v 414 +/- 36 pg/mL).(ABSTRACT TRUNCATED AT 250 WORDS)