Effect of low intravenous doses of TRH, acid‐TRH and cyclo(His‐Pro) on cerebral and peripheral blood flows

Koskinen, Lars‐Owe D.

doi:10.1111/j.1476-5381.1986.tb10193.x

Cited by 40 publications

(16 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this respect, our data are in agreement with a recent report showing decreases in gastrointestinal and renal blood flow (measured by microspheres) after systemic injections of TRH in the conscious rabbit. 37 The blood flow to skeletal muscles, however, was not affected by TRH in the rabbit.…”

Section: Discussionmentioning

confidence: 99%

Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat.

Sirén

Lake

Feuerstein

1988

Circulation Research

View full text Add to dashboard Cite

Tbe mechanisms mediating the etl'ects ofthyrotropin-releasing hormone (TRH) on the cardiovascular system were studied in the conscious rat. Intracerebroventricolar (i.c. v.) injection of TRH (8 pmol-80 nmollkg) induced dose-dependent lncreases in mean arterial pressure, heart rate, and cardiac index. Rindquarter blood Oow increased due to vasodilation, while an lncrease in renal and mesenteric vascular resistance caused a decrease in blood Oow in the respective organs. The plasma Ievels of norepinephrine a~d epinephrine were increased by TRH, while there was no change in plasma renin activity or vasopressin. Tbe cardiovascular actions of i.c. v. TRH were not in.fluenced by blockade of the renin-angiotensin system or vasopressin receptors. Tbe ganglion blocker chlorisondamine and the a 1 -aod al-adrenoreceptor antagooist phentolamlne (2 mg/kg i.v.) abolished the increase in blood pressure and mesenteric vasoconstriction after i.c. v. TRH. Propranolol (2 mg/kg i. v.) blocked the TRH-ioduced increase in cardiac index, heart rate, and hindquarter blood flow. The hindquarter vasodllatlon lnduced by TRH was also blocked by the selective ß 1 -adrenocept9r antagonist ICI 188,551(1 or 2 mg/kg i.v.), while tbe ,8,-adrenoceptor blocker practolol (10 mg/kg i.v.) had no eft'ect on the hindquarter vasodiJation produced by TRH but totally blocked the increase in cardiac Index. In adrenal demedullated rats, the systemic hemodynamic eft'ects ofi.c. v. TRH were dimlnished along with the decrease in renal blood flow and lncrease in renal vascular resistance; however, the iocrease in hfndquarter blood flow was attenuated only in adrenal demedullated rats pretreated with the sympathetlc blocker bretylium. The renal vasoconstriction induced by i.c. v. TRH was not abolished by renal denervation. In sinoaortic debufl'ered rats, the pressor, tachycardic, and mesenteric vasoconstrictor responses to centrally administered TRH were significantly potentiated. Taken together, these data soggest that the putative rieurotransmitter TRH may play a role in central regulation of cardiac functions and organ blood flow distribution through both tbe sympathetic nerves and the adrenal medulla. A pivotal roJe for ß 1 -adrenoceptors in mediation ofhindquarter vasodilation ls also demonstrated. (Circulatlon Research 1988;62:139-154) T . hyrotropin·releasing hormone (TRH, L·pyro-glutamyl·L-histidyl-L·prolinamide) was the first hypothalamic releasing factor to be isolated, chemically characterized, and synthesized (for review, see Prasad 1 ). In addition to its endocrine actions (thyrotropin, prolactin, and growth hormone release), TRH elicits multiple autonomic effects (e.g., arousal, analeptic effect, increased locomotor activity, and changes in body temperature, respiration, blood pressure, and heart rate) that are unrelated to its action on the hypothalamic pituitary axis (for review, see Horita et al,2 Griffiths, 3 and Prasad'). Thus, cardiorespiratory responses to intracerebroventricularly (i.c. v.) administered TRH have been reported in hypophys...

show abstract

Section: Discussionmentioning

confidence: 99%

Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat.

Sirén

Lake

Feuerstein

1988

Circulation Research

View full text Add to dashboard Cite

show abstract

“…There is evidence for the involvement of endogenous TRH in the regulation of blood pressure in spontaneously hypertensive rats (Nurminen, 1992). In the rabbit, TRH elicits both vasoconstriction in the gastric mucosa, pancreas and spleen and vasodilatation in the brain (Koskinen, 1986b;Seligsohn, 1992a). The vasoconstriction in the rabbit seems mainly to be due to an a,-adrenoceptor mechanism (Seligsohn & Koskinen, 1991).…”

Section: Discussionmentioning

confidence: 99%

Effects of N^G‐nitro‐l‐arginine methyl ester on the cardiovascular system of the anaesthetized rabbit and on the cardiovascular response to thyrotropin‐releasing hormone

Seligsohn

Bill

1993

British J Pharmacology

View full text Add to dashboard Cite

1 The effects of 300 mg kg-' of the nitric oxide (NO) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on the regional blood flow, on the flow response to 1 mg kg-' of thyrotropin-releasing hormone (TRH) and on cerebral blood flow autoregulation were studied in urethane anaesthetized rabbits subjected to unilateral sectioning of the cervical sympathetic chain. The blood flow measurements were performed by the tracer microspheres method. 2 The cerebral arteriovenous difference in oxygen saturation (CAVOD) was measured before and after the administration of L-NAME and TRH in order to ascertain whether the effects on cerebral blood flow that were observed were secondary to changes in cerebral metabolism. 3 L-NAME caused a significant decrease in blood flow in several cerebral regions; CBF,O, decreased to 72 ± 4% of control (P < 0.001). An increase in blood pressure and a concurrent decrease in heart rate and cardiac output were noted. 4 In the eye, L-NAME caused a reduction in uveal blood flow which was more pronounced on the sympathetically intact side; in the retina the blood flow decreased to 50% of control on both sides. 5 The administration of TRH in animals pretreated with L-NAME caused a significant increase in blood pressure and cerebral blood flow. 6 In L-NAME-treated animals the CBF was not affected when the mean arterial blood pressure was increased by ligation of the abdominal aorta. 7 The CAVOD increased from 56.0 ± 5.2 to 73.6 ± 3.5%, 20 min after the administration of L-NAME.In animals given 1 mg kg-' TRH after L-NAME the CAVOD decreased to 54.6 ± 4.6%, 5 min after the injection of TRH. 8 The results of the present study indicate that endogenous NO is involved in the regulation of regional blood flow and blood pressure in the anaesthetized rabbit. The reduction in cerebral blood flow that was caused by L-NAME was not due to a reduction in cerebral metabolism. An interaction between the NO synthesis/release/effect and the sympathetic nervous system was found in the uvea. There was no evidence for a major involvement of NO in the cardiovascular responses to TRH and autoregulation of cerebral blood flow was not abolished by L-NAME.

show abstract

“…Thirty minutes after injury, cultures were washed again and incubated with 35b or vehicle, as appropriate, for 16 to 18 hours. may increase cerebral blood flow (Koskinen, 1986;Prasad, 1995), and it may have antioxidant activity (Prasad, 1995;Shvachkin et al, 1989). This dipeptide, however, does not appear to have any nootropic activity and may even disrupt some forms of learning Sahgal, 1983, 1984;Prasad, 1995).…”

Section: Fig 13mentioning

confidence: 99%

Novel Diketopiperazine Enhances Motor and Cognitive Recovery after Traumatic Brain Injury in Rats and Shows Neuroprotection In Vitro and In Vivo

Faden

Knoblach

Černak

et al. 2003

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Summary:The authors developed a novel diketopiperazine that shows neuroprotective activity in a variety of in vitro models, as well as in a clinically relevant experimental model of traumatic brain injury (TBI) in rats. Treatment with 1-ARA35b (35b), a cyclized dipeptide derived from a modified thyrotropin-releasing hormone (TRH) analog, significantly reduced cell death associated with necrosis (maitotoxin), apoptosis (staurosporine), or mechanical injury in neuronalglial cocultures. Rats subjected to lateral fluid percussioninduced TBI and then treated with 1 mg/kg intravenous 35b thirty minutes after trauma showed significantly improved motor recovery and spatial learning compared with vehicle-treated controls. Treatment also significantly reduced lesion volumes as shown by magnetic resonance imaging, and decreased the number of TUNEL-positive neurons observed in ipsilateral hippocampus. Unlike TRH or traditional TRH analogs, 35b treatment did not change mean arterial pressure, body temperature, or thyroid-stimulating hormone release, and did not have analeptic activity. Moreover, in contrast to TRH or typical TRH analogs, 35b administration after TBI did not alter freemagnesium concentration or cellular bioenergetic state. Receptor-binding studies showed that 35b did not act with high affinity at 50 classical receptors, channels, or transporters. Thus, 35b shows none of the typical physiologic actions associated with TRH, but possesses neuroprotective actions in vivo and in vitro, and appears to attenuate both necrotic and apoptotic cell death.

show abstract

Effect of low intravenous doses of TRH, acid‐TRH and cyclo(His‐Pro) on cerebral and peripheral blood flows

Cited by 40 publications

References 38 publications

Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat.

Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat.

Effects of N^G‐nitro‐l‐arginine methyl ester on the cardiovascular system of the anaesthetized rabbit and on the cardiovascular response to thyrotropin‐releasing hormone

Novel Diketopiperazine Enhances Motor and Cognitive Recovery after Traumatic Brain Injury in Rats and Shows Neuroprotection In Vitro and In Vivo

Contact Info

Product

Resources

About

Effect of low intravenous doses of TRH, acid‐TRH and cyclo(His‐Pro) on cerebral and peripheral blood flows

Cited by 40 publications

References 38 publications

Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat.

Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat.

Effects of NG‐nitro‐l‐arginine methyl ester on the cardiovascular system of the anaesthetized rabbit and on the cardiovascular response to thyrotropin‐releasing hormone

Novel Diketopiperazine Enhances Motor and Cognitive Recovery after Traumatic Brain Injury in Rats and Shows Neuroprotection In Vitro and In Vivo

Contact Info

Product

Resources

About

Effects of N^G‐nitro‐l‐arginine methyl ester on the cardiovascular system of the anaesthetized rabbit and on the cardiovascular response to thyrotropin‐releasing hormone