Effect of low intravenous doses of TRH, acid-TRH and cyclo(His-Pro) on cerebral and peripheral blood flows.
Local cerebral and peripheral blood flow in conscious and anaesthetized rabbits were investigated with the microsphere method, before and after the i.v. administration of 25 or 50 micrograms kg-1 thyrotropin-releasing hormone (TRH). Before the experiment, the cervical sympathetic chain was sectioned on one side in order to evaluate the possible effect of the sympathetic nerves on cranial and extracranial blood flows. Blood flow was also determined in anaesthetized rabbits before and after the administration of the TRH metabolites cyclo(His-Pro) and acid-TRH and after subsequent administration of 50 micrograms kg-1 TRH. TRH caused an increase in mean arterial blood pressure (MAP) of about 1 to 2 kPa whereas cyclo(His-Pro) and acid-TRH had no effect on MAP. In the anaesthetized animal an increase in total cerebral blood flow (CBFtot), from 71 +/- 7 to 107 +/- 12 g min-1 100 g-1 (P less than 0.05) was observed on the sympathetic intact side after 25 micrograms kg-1 TRH and a further increase to 130 +/- 9 g min-1 100g-1 (P less than 0.01) after 50 micrograms kg-1 TRH. A similar effect was observed on the sympathotomized side. An effect on CBF in the conscious animal was not detected. The control CBFtot (104 +/- 8 g min-1 100g-1) was higher in these animals than in the anaesthetized animals (P less than 0.02). Neither cyclo(His-Pro) nor acid-TRH mimicked the effect of TRH on CBF. In several peripheral tissues, e.g. skin, pancreas and gastric mucosa, a reduction in blood flow was noted after the administration of TRH in both anaesthetized and conscious rabbits. It was concluded that TRH can induce cerebral vasodilatation in animals with a depressed CBF, whereas the vasoconstrictor effect of TRH in peripheral organs is not markedly affected by the state of consciousness.
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*
D010456:Peptides, Cyclic; D010879:Piperazines; C020271:thyrotropin-releasing hormone, deamido-; D013973:Thyrotropin-Releasing Hormone; C015924:histidyl-proline diketopiperazine; D011761:Pyrrolidonecarboxylic Acid