Endogenous opioid peptides and blood pressure regulation during controlled, stepwise hemorrhagic hypotension.

In the present study, the role of the endogenous opioid peptide systems in the regulation of blood pressure during standardized, stepwise hemorrhagic hypotension was investigated in anesthetized rats. Central as well as peripheral administration of naloxone resulted in an increase in the bleeding volumes required to reduce blood pressure. Bleeding volumes also increased after the peripheral injection of naloxone methobromide, an analog of naloxone that does not readily cross the blood-brain barrier. Following central administration of antisera against beta- and alpha-endorphin and dynorphin A(1-13), the amount of blood that had to be withdrawn to induce hypotension was elevated. In rats treated with an antiserum against [Met5] enkephalin or gamma-endorphin, bleeding volumes did not differ from those of rats treated with control serum. These data indicate that activation of central and possibly also of peripheral opiate receptors plays a role in the control of blood pressure during blood loss. Dynorphin A(1-13), beta- and alpha-endorphin, or closely related peptides might be the endogenous ligands for the receptors that are blocked by naloxone.

Beta-endorphin and central control of arterial blood pressure during challenge of circulatory homeostasis.

A variety of neurotransmitters and neuropeptides appear to participate in the central control mechanisms of arterial blood pressure. Our knowledge of these mechanisms is limited as yet. In the present study the involvement of the opioid peptide beta-endorphin in circulatory homeostasis was studied. Under conditions in which beta-endorphin does not affect basal blood pressure and heart rate this peptide had a pronounced prohypotensive influence in normotensive rats. This was found for two conditions during which circulatory homeostasis was challenged. Firstly, during blood letting in a rat model employed to test blood pressure regulation during hemorrhage, and secondly, for the central hypotensive action of alpha-methyldopa. In the first model hypotension was produced by stepwise bleeding to respectively 80, 60 and 40 mmHg mean arterial pressure. Intracerebroventricular (i.c.v.) administration of an antiserum raised against beta-endorphin or of naloxone (s.c. or i.c.v.) caused a significant increase in the required bleeding volume, whereas an opposite action was observed after the injection of morphine (s.c.) or of beta-endorphin (i.c.v.). The role of beta-endorphin in the hypotensive action of alpha-methyldopa, given intracisternally (i.c.) was evaluated in conscious rats equipped with chronic cannulas. Pretreatment with the opiate antagonist naltrexone (i.c.) caused an inhibition of the hypotension and bradycardia induced by alpha-methyldopa. This effect of the receptor antagonist was mimicked by i.c. administration of a beta-endorphin antiserum. Taken together, these data point to a hypotensive influence exerted by endogenous beta-endorphin under conditions during which circulatory homeostasis are challenged.

Central and peripheral opiate receptors appear to be activated during controlled haemorrhagic hypotension.

The present study investigated the question of whether peripheral or central opiate receptors are activated during controlled haemorrhagic hypotension. In anaesthetized Wistar rats, blood pressure was reduced by steps, by bleeding, to 80, 60 and 40 mmHg. Subcutaneous administration of 1 mg/kg of naloxone and of methyl naloxone-Br, an analogue of naloxone, which does not readily cross the blood-brain barrier, significantly elevated the bleeding volume at the 40-mmHg blood pressure level. A dose of 10 mg/kg of methyl naloxone-Br had no effect on the bleeding volume. We therefore conclude that during haemorrhage, endogenous opioid peptides activate both central and peripheral opiate receptors, thereby exerting a hypotensive influence.

Influence of centrally administered alpha- and gamma 2-melanocyte-stimulating hormone on hypothalamic blood flow autoregulation in the rat.

The effect of intracerebroventricularly (i.c.v.) administered alpha-melanocyte-stimulating hormone (MSH) and gamma 2-MSH on hypothalamic blood flow autoregulation was studied in anesthetized rats at different levels of standardized arterial hypotension. Autoregulation was impaired upon i.c.v. administration of 5 micrograms/kg gamma 2-MSH while alpha-MSH caused no changes. Since this effect of gamma 2-MSH was identical to that produced by i.c.v. naloxone in the same model, gamma 2-MSH may be a functional antagonist of central opioid mechanisms participating in the control of cerebral blood flow autoregulation.

Continuous measurement of cerebral blood volume in rats with the photoelectric technique: effect of morphine and naloxone.

The validity of a photoelectric method for continuous cerebral blood volume (CBV) measurement was tested and modified for the rat's brain. A new way of introducing a miniature light source between the two hemispheres and fixing a light sensitive silicone blue cell to the outer surface of the parietal bone was developed. Light extinction factor of the rat's blood was determined experimentally (Eb rat = 1.38 +/- 0.15) in order to calculate absolute CBV value in this species, resulting in a 4.77 +/- 0.13 vol % absolute CBV value. Data obtained in anesthetized, artificially ventilated rats by simultaneous recording of CBV and local cerebral blood flow (H2-gas clearance technique) show that local hypothalamic blood flow decreased significantly after morphine (1.0 mg/kg s.c.), while total CBV remained unchanged. Opiate receptor blockade with naloxone (1.0 mg/kg s.c.) on the contrary, as well as naloxone and morphine administration, caused no change in local hypothalamic blood flow, but resulted in a significant increase of total cerebral blood volume.