EVIDENCE FOR A SODIUM-INDUCED ACTIVATION OF CENTRAL NEUROGENIC MECHANISMS IN ONE-KIDNEY, ONE-CLIP RENAL HYPERTENSIVE RATS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 223  (2) , 510-515
Abstract
The mechanisms sustaining high blood pressure in conscious 1-kidney, 1-clip Goldblatt rats were evaluated with the use of SK&F 64139 [7-8 dichloro-1,2,3,4-tetrahydroisoquinoline hydrochloride], a phenylethanolamine N-methyltransferase inhibitor capable of crossing the blood-brain barrier, and captopril, an angiotensin-converting enzyme inhibitor. The rats were studied 3 wk after left renal artery clipping and contralateral nephrectomy. During the developmental phase of hypertension, 2 groups of rats were maintained on a regular salt (RNa) intake, whereas 2 other groups were given a low-salt (LNa) diet. On the day of the experiment, the baseline mean blood pressure of the LNa rats (177.4 .+-. 5.2 mm Hg, mean .+-. SE, n = 15) was similar to that of 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 < 0.001) 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. Captopril (10 mg p.o.) normalized blood pressure in LNa rats (n = 8) but produced only a 13.4-mm Hb blood pressure drop in RNa rats (n = 8). RNa rats treated with SK&F 64139 had 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. In this experimental model of hypertension, Na+ 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.