1. The blood pressure effect of SKF 64139, a phenylethanolamine N-methyltransferase (PNMT) inhibitor acting both in the central and peripheral nervous system, was studied in conscious normotensive and glucocorticoid-hypertensive rats maintained for 2 weeks on a salt-deficient diet. On the day of the experiment, mean blood pressure was 119.2 ± 1.1 mmHg (mean ± sem) in the normotensive and 143.2 ± 1.9 mmHg (P < 0.001) in the hypertensive rats. In all animals, the blood pressure was followed for 4 h after oral gavage by either SKF 64139 (50 mg/kg) or its vehicle (5% glucose solution).
2. In the vehicle-treated rats, no change in blood pressure occurred. However, after SKF 64139 administration, a 17.9 ± 3.8 mmHg (P < 0.001) blood pressure fall was observed in the hypertensive rats whereas normotensive animals did not decrease their pressure.
3. Plasma catecholamines were determined in all these rats at the end of the observation period. No significant difference in plasma noradrenaline and adrenaline levels was observed between normotensive and hypertensive as well as vehicle- and SKF 64139-treated rats, though both catecholamines tended to be higher after administration of the PNMT inhibitor.
4. In two additional groups of glucocorticoid-hypertensive rats, the blood pressure effects of an infusion of saralasin, a competitive antagonist of angiotensin II, or of a bolus injection of a vasopressin analogue antagonizing the pressor action of vasopressin, were investigated over a 20 min period.
The vasopressin antagonist had no blood pressure effect whereas saralasin decreased mean blood pressure from 144 ±1.9 to 136 ± 3.2 mmHg (P < 0.005).
5. These data suggest that the sympathetic nervous system is the main vasoconstrictor system involved in the maintenance of established glucocorticoid hypertension. Since SKF 64139 is also known to inhibit to some degree α-adrenoceptors, monoamine oxidase and neuronal uptake processes, it remains unclear, however, whether the blood pressure-lowering effect of this PNMT inhibitor can be attributed to central blockade of adrenaline synthesis.
