Dietary protein intake influences the antihypertensive potency of methyldopa in spontaneously hypertensive rats

When spontaneously hypertensive rats consumed a single meal before receiving methyldopa (MD), the increase in brain MD levels and the blood pressure reduction varied inversely with the meal's protein content. MD injection elicited a greater reduction in blood pressure (and a larger rise in brain MD) in spontaneously hypertensive rats consuming a protein-free meal than in fasting animals; it induced a smaller fall in blood pressure (and a smaller increase in brain MD) in spontaneously hypertensive rats ingesting a protein-containing meal than in fasting animals. This effect may depend on the large neutral amino acids contained in protein. Ingestion of a food identical in amino acid content of 18% casein, but containing an amino acid mixture instead of protein, also blunted the MD-induced fall in blood pressure. However, consumption of a similar diet, lacking the large neutral amino acids (but not other amino acids), elicited an MD-induced blood pressure reduction similar to that caused by ingesting a protein-free diet. The combined effects of meal consumption and MD injection on brain MD and blood pressure correlated significantly with the serum ratio of MD to the sum of the natural large neutral amino acids and not with serum MD alone. Similar effects were also noted with chronic dietary and MD treatment. Thus, dietary protein content can influence significantly the potency of a clinically important amino acid drug that acts within the brain.