The mechanisms sustaining
high blood pressure in conscious one-kidney, one-
clip Goldblatt rats were evaluated with the use of
SK&F 64139, a
phenylethanolamine N-methyltransferase inhibitor capable of crossing the blood-brain barrier and of
captopril, an
angiotensin converting enzyme inhibitor. The rats were studied 3 weeks after left renal artery clipping and contralateral
nephrectomy. During the developmental phase of
hypertension, two groups of rats were maintained on a regular
salt (
RNa) intake, whereas two other groups were given a low
salt (LNa) diet. On the day of the experiment, the base-line mean blood pressure measured in the LNa rats (177.4 +/- 5.2 mm Hg, mean +/- S.E., n = 15) was similar to that measured in the
RNa rats (178.7 +/- 5.4 mm Hg, n = 16).
SK&F 64139 (12.5 mg p.o.) induced a significantly more pronounced (P less than .001) blood pressure decrease in the
RNa rats (-25.6 +/- 3.6 mm Hg, n = 8) than in the LNa rats (-4.3 +/- 3.3 mm Hg, n = 7) during a 90-min observation period. On the other hand,
captopril (10 mg p.o.) normalized blood pressure in LNa rats (n = 8), but produced only a 13.4 mm Hg blood pressure drop in
RNa rats (n = 8).
RNa rats treated with
SK&F 64139 were found to have decreased
phenylethanolamine N-methyltransferase activity by an average 80% in selected brain stem nuclei when compared with nontreated rats. No significant difference in plasma
catecholamine levels was found between the
RNa and LNa rats. These results suggest that, in this experimental model of
hypertension, the
sodium ion might increase the model of
hypertension, the
sodium ion might increase the
vasoconstrictor contribution of the sympathetic system via a centrally mediated neurogenic mechanism while at the same time it decreases the
renin-dependency of the
high blood pressure.