Saitongdee, Porncharn; (1999) Cardiovascular changes during and after arousal from hibernation in golden hamsters. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis examines the plasticity of cardiovascular control of golden hamsters {Mesocricetus auratus) in four physiological conditions, normal controls at euthermy, cold controls (cold-exposed animals that did not undergo hibernation), hibernating animals and animals aroused from hibernation for 2 h. There were two main areas of study 1) the endothelium and perivascular innervation of mesenteric and renal arteries using electron-immunocytochemical techniques and 2) gap junctions in the left ventricle and aorta using immunohistochemistry combined with laser confocal microscopy. During hibernation, the percentages of both nitric oxide synthase (NOS)- positive and endothelin (ET)-positive endothelial cells in the superior mesenteric artery and renal artery were markedly lower than in the controls. In the mesenteric artery, the percentage of NOS and ET positive endothelial cells fell from 22% and 17%, respectively, in the normal controls to 1% and 6%, respectively, during hibernation. In the renal artery 23% and 43% of endothelial cells contained NOS and ET, respectively in the normal controls but only 5% contained NOS and ET in the hibernating group. On arousal, the percentages of NOS and ET immunopositive endothelial cells were similar to the normal control values (18% and 13%, respectively, in the mesenteric artery and 21% and 30%, respectively, in the renal artery). In perivascular nerves, there was an increase in the percentage of axon profiles positive for sympathetic nerve markers, tyrosine hydroxylase (from 17% to 57% during hibernation in the mesenteric artery and from 20% to 76% during hibernation in the renal artery) and neuropeptide Y (from 30% to 65% during hibernation in the mesenteric artery and from 25% to 77% in the renal artery). There was also a hibernation-associated decrease in the percentage of axon profiles containing a parasympathetic nerve marker, vasoactive intestinal polypeptide (from 14% to 4% during hibernation) in the mesenteric artery. These changes are consistent with increased peripheral vascular resistance during hibernation. The endothelial and neural changes reported may reflect a predominantly sympathetic vasoconstrictor control during hibernation concomitant with a reduced endothelial contribution to the maintenance of vascular tone. The density of immunoreactive connexin (Cx) 43 gap junctions was significantly increased in left ventricular cardiomyocytes in hibernating hamsters (area and numerical density were 9.73±1.4 and 16.11 ±1.6 µm2/1000 µm2, respectively, in hibernation compared to 4.03±0.93 and 10.68±1.7 µm2/1000 µm2 in normal control, hibernation compared to 4.03±0.93 and 10.68±1.7 µm2/1000 in normal control, P<0.05). Cx43 plaque size was larger in cold controls and hibernating animals (0.52+0.04 and 0.58±0.03 µm2, respectively, compared to normal controls, P<0.05). Cx40 immunoexpression at the endothelium lining coronary arterioles of the ventricle was increased in the cold control group only: Cx40 area density was 38.99±4.19 µm2/1000 µm2 in cold controls compared to 25.26±3.2 µm2/1000 µm2 in normal controls and was significantly greater than during hibernation (23.04±3.1 µm2/1000 µm2, P<0.05). There were no changes in Cx40 levels in the aortic endothelium or in levels of Cx43 in smooth muscle of the aorta. The increase in cardiomyocyte gap junction proteins in the cold controls may represent a compensatory response to prepare the animal for hibernation avoiding ventricular fibrillation, while during hibernation, increased connexin expression may facilitate intercellular transfer of selected signals in readiness for arousal. The elevation of gap junction channels in coronary arteriolar endothelium corresponds with the requirement of increased intercellular communications during the prolonged circulatory changes required to maintain core temperature. In summary, cardiovascular changes during hibernation operate at several different levels, neural, endothelial and at the level of cell to cell communication via gap junctions. These changes emphasise the active rather than passive nature of the process of hibernation and arousal.

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