Alterations In Arterial Reactivity Of Various Arteries In Rats Under Two Haemodynamic States

Cardiovascular disease is one of the most challening diseases in modernworld.The change of haemodynamic states significantly affects arterial structureand function.The hemokinesis in artery has great relationship with pathogenesis ofcardiovascular disease,such as artherosclerosis, thrombogenesis, heart infarction,hypertension and coronary artery disease.Alterations of pressure, velocity, andshear stress in artery result in pathological change of vessel wall,throughinfluencing adaptable mechanism of vascular smooth muscle cell and endothelialcell.Hyperthyroidism causes increased pressure,high speed and big shear stresswithin the arterial blood flow region.Whereas simulated weightlessness leadscoronary system to low perfusion pressure, reducing blood flow, therefore withinthe coronary arterial blood flow region it causes decreased pressure,low speed andsmall shear stress. But there is no in-depth and systematic research about therelationship between these high or low haemodynamic states and cardiovasculardisease.So we can get a better understanding of cardiovascular diseasepathogenesis through in-depth and systematic study of alterations in arterialreactivity under different haemodynamic states. AIMAIMS Through studying alterations in arterial reactivity of various arteriesin rats under hingh haemodynamic state of hyperthyroidism and lowhaemodynamic state of simulated weightlessness,to understand the pathogenesisof cardiovascular disease and the mechanism of orthostatic intolerance after spaceflight.METHODS Established hyperthyroid rat model and simulated weightlessnessrat model. By means of isolated arteries ring technology,studied alterations inarterial reactivity of renal artery,mesenteric artery,femoral artery,carotidartery,basilar artery, small mesenteric branches artery in hyperthyroid rats andcoronary artery in simulated weightlessness rats. Using light microscopy andelectron microscopy,observed morphology and ultrastructure changes of coronaryartery of simulated weightlessness rats.The eNOS and iNOS protein expressionswere observed by Western Blot technique.RESULTS1,The isometric contractile tensions evoked by KCl(10～100 mmol/L)andphenylephrine (PE) (10-9～10-4 mol/L)were significantly lower in renalarterial,mesenteric arterial,femoral arterial,carotid arterial rings from hyperthyroidrats compared with those of control ones (P<0.05). The vasodilator responseinduced by acetylcholine (ACh) (10-9～10-4 mol/L)was significantly increased inhyperthyroid group (P<0.05). But the differences of responses of those arterialrings induced by sodium nitroprusside (SNP) (10-9～10-4 mol/L)between twogroups were nonsignificant. The sensitivities of those arterial rings to KCl andACh were significantly enhanced by hyperthyroidism (P<0.05), whereas thesensitivity to PE and SNP did not show any significant differences between twogroups. 2,The isometric contractile tensions evoked by KCl and 5-HT or PE weresignificantly lower in basilar and small mesenteric branch arterial rings fromhyperthyroid rats compared with those of control ones (P<0.05). The vasodilatorresponse induced by ACh was significantly increased in hyperthyroid group(P<0.05). But the differences of responses of those arterial rings induced bysodium SNP between two groups were nonsignificant. The sensitivities of thosearterial rings to KCl and ACh were significantly enhanced by hyperthyroidism(P<0.05), whereas the sensitivity to 5-HT or PE and SNP did not show anysignificant differences between two groups.3,The eNOS protein expression increased in basilar and small mesentericbranch artery of hyperthyroid rats compared with those of control ones (P<0.05).The iNOS protein expression occured in hyperthyroid rats but didn't occure incontrol ones.4,The isometric contractile tensions evoked by KCl and PE weresignificantly lower in coronary arterial rings from two weeks simulatedweightlessness rats compared with those of control ones (P<0.05). The vasodilatorresponse induced by ACh and SNP were significantly decreased in simulatedweightlessness group (P<0.05).The sensitivities of those arterial rings to KCl andACh were significantly decreased by simulated weightlessness (P<0.05), whereasthe sensitivity to PE and SNP did not show any significant differences betweentwo groups..5,Morphology and ultrastructure changes of coronary arteries of two weekssimulated weightlessness rats were observed: pathological changes took place invascular endothelial cells and vascular smooth muscle was atrophical.6,The eNOS protein expression decreased in coronary arteries of two weeks simulated weightlessness rats compared with those of control ones (P<0.05). TheiNOS protein expression didn't occure in two groups.CONCLUSION The high haemodynamic state of hyperthyroidism maybethrough influencing adaptable mechanism of vascular smooth muscle cell andvascular endothelial cell caused arteriel vasoconstriction weaken and theendothelium-dependent vasodilator response increase.The vascular endotheliumdependentvasodilation increased under high haemodynamic state maybe bymeans of the enhancement of NO. The low haemodynamic state of simulatedweightlessness significantly affected coronary arterial structure and function.Thecoronary arterial vasoconstriction and vasodilator response both decreased, andpathological changes took place in vascular endothelial cells and vascular smoothmuscle cells.This change may paly a role in pathogenesis of cardiovasculardisease and the mechanism of orthostatic intolerance after space flight.