Comparison among the effects of arginine, a nitric oxide precursor, isosorbide dinitrate and molsidomine, two nitric oxide donors, on hormonal secretions and blood pressure in man.
Arginine has well-known stimulatory effects on GH, PRL and insulin secretion in man but the mechanisms underlying these effects are still unclear. More recently, it has been demonstrated that arginine is the precursor of nitric oxide (NO) which mediates its vasodilatatory effect. Thus, it has been hypothesized that NO could also mediate the hormonal effects of arginine. To clarify this point, in seven normal young volunteers (7 normal male subjects, age 26-35 yr) we compared the effects of arginine hydrochloride (ARG, 0.5 g/kg iv over 30 min) on GH, PRL, insulin and glucose levels as well as on blood pressure, with those of isosorbide dinitrate (ISDN, 5 mg po) and molsidomine (MOLS, 4 mg po), two NO donors which possess well-known vasodilatatory effects. ARG infusion elicited a clear-cut GH increase (peak vs baseline 17.6 +/- 4.7 vs 2.7 +/- 0.8 (g/L, p < 0.01), PRL (20.6 +/- 2.8 vs 6.9 +/- 0.5 (g/L, p < 0.01) and insulin levels (31.4 +/- 5.7 vs 4.5 +/- 2.1 (U/L, p < 0.01) while induced a biphasic variation of plasma glucose levels with early increase (p < 0.01), followed by late decrease below basal values (p < 0.01). On the other hand, blood pressure was decreased by ARG (nadir vs baseline; systolic: 103 +/- 6 vs 112 +/- 3, p < 0.02 and diastolic 61 +/- 4 vs 72 +/- 2 mmHg, p < 0.02, respectively). ISDN and MOLS did not modify basal GH, PRL and insulin as well as glucose levels while induced a clear reduction in blood pressure (ISDN: nadir vs baseline; systolic: 94 +/- 4 vs 112 +/- 2, p < 0.02; diastolic 69 +/- 3 vs 80 +/- 2, p < 0.02; MOLS: systolic: 94 +/- 3 vs 113 +/- 2 p < 0.02; diastolic 63 +/- 4 vs 72 +/- 2, p < 0.02). The lowering effect of both ISDN and MOLS on both systolic and diastolic blood pressure levels was higher than that induced by ARG. The effect of the latter was, in turn, significantly different from that of placebo on diastolic levels only. In conclusion, our present date are against the hypothesis that NO mediates the stimulatory effects of arginine on GH, PRL and insulin secretion. On the other hand, our findings agree with the hypothesis that ARG has NO-mediated vasodilatatory effect able to decrease blood pressure in man.
Maccario
M
M
Dipartimento di Medicina Interna, Università di Torino, Italy.
Oleandri
S E
SE
Procopio
M
M
Grottoli
S
S
Avogadri
E
E
Camanni
F
F
Ghigo
E
E
D000328:Adult; D001120:Arginine / Q000009:adverse effects / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D006728:Hormones / Q000097:blood*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008981:Molsidomine / Q000009:adverse effects / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000494:pharmacology*
D001786:Blood Glucose; D006728:Hormones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001120:Arginine; D008981:Molsidomine; D007548:Isosorbide Dinitrate