THE ACUTE CARDIOVASCULAR ACTIONS OF INTRAVENOUS THYROTROPIN-RELEASING-HORMONE (TRH) IN MAN ARE MEDIATED BY NONCATECHOLAMINERGIC MECHANISMS

1 Intravenous bolus doses of thyrotrophin releasing hormone (TRH, 50-1 000 mu g) caused statistically significant, non-dose dependent and tra nsient rises in blood pressure, heart rate and plasma catecholamines i n healthy young males. 2 Mean peak incremental rises in systolic blood pressure (mean +/- s.e. mean) following 50, 200 and 500 mu g TRH were 14.3 +/- 2.9 mmHg, 15.7 +/- 3.2 mmHg and 17.1 +/- 3.9 mmHg respective ly (all P < 0.05 vs placebo). Mean incremental rises in heart rate for the three doses of TRH were 8.2 +/- 2.2 beats min(-1), 7.1 +/- 1.8 be ats min(-1), and 10.7 +/- 2.9 beats min(-1) respectively (all P < 0.05 vs placebo). 3 Following the 50 mu g and 1000 mu g doses of TRH, plas ma noradrenaline and adrenaline rose significantly (P < 0.05) between 4 and 8 min. Mean +/- s.e. mean incremental plasma noradrenaline rise following 50, 200 and 1000 mu g TRH were 0.4 +/- 0.13 nmol l(-1), 0.37 +/- 0.21 nmol l(-1) and 0.41 +/- 0.18 nmol l(-1) respectively. Mean /- s.e. mean incremental rise in adrenaline for the 50, 200 and 1000 m u g dose were 0.13 +/- 0.04 nmol l(-1), 0.08 +/- 0.03 nmol l(-1), and 0.11 +/- 0.05 nmol l(-1) respectively. 4 Following administration of t he ganglion blocking drug pentolinium (5 mg) the incremental systolic blood pressure and heart rate rises following 500 mu g TRH alone 16.6 +/- 2.8 mmHg and 10.4 +/- 3.1 beats min(-1) respectively. 5 The rises in plasma noradrenaline and adrenaline following TRH were attenuated b y prior ganglion blockade. 6 alpha-adrenoceptor blockade with thymoxam ine (0.3 mg kg(-1) bolus + 0.3 mg kg(-1) h(-1) infusion), singly and c ombined with intravenous propranolol (10 mg i.v. over 10 min), did not alter the presser or tachycardic effects of 500 mu g TRH. 7 In conclu sion, although plasma noradrenaline rises following i.v. TRH, suggesti ng activation of the sympathetic nervous system, this effect is not re sponsible for the presser response to TRH, which appears to be due to either a direct vasoconstrictive effect on the peripheral resistance v essels or a direct inotropic/chronotropic effect on the heart.