Role of hyperglycaemia in the pathogenesis of hypotension observed in type-1 diabetic rats.
The role of hyperglycaemia in the pathogenesis of hypotension in diabetic disorders was investigated using the changes in cardiac M(2)-muscarinic receptor (M(2)-mAChR) gene expression in type-1-like diabetic rats and cultured cardiomyocytes. Blood pressure was markedly decreased in diabetic rats following the intravenous injection of streptozotocin (STZ) for 8 weeks. Also, the baroreflex sensitivity (Delta HR/Delta BP), as measured by the changes in heart rate (Delta HR) and mean blood pressure (Delta BP) 1 min after the intravenous injection of phenylephrine (10 microg/kg), was significantly increased. Arecaidine propargyl ester (APE), a M(2)-mAChR agonist produced a marked reduction in heart rate in these diabetic rats. Normalization of plasma glucose in diabetic rats using insulin (0.5 IU) or phlorizin (1 mg/kg) injection attenuated the blood pressure reduction and reversed the mRNA and protein levels of cardiac M(2)-mAChR. A high concentration of glucose (20 mmol/l) directly influenced the increase in gene expression of M(2)-mAChR in the H9c2 cardiac cell line. Hyperglycaemia induced an increase in cardiac M(2)-mAChR gene expression, suggesting a role in the pathogenesis of hypotension in diabetic disorders.
Liu
I-Min
IM
Department of Pharmacy, Tajen University, Yen-Pou, Ping Tung Shien, Taiwan.
Chang
Cheng Kuei
CK
Juang
Shiow-Wen
SW
Kou
Dai-Huang
DH
Tong
Yat-Ching
YC
Cheng
Kai-Chun
KC
Cheng
Juei-Tang
JT
D000818:Animals; D001115:Arecoline / Q000031:analogs & derivatives / Q000494:pharmacology; D017704:Baroreflex; D002460:Cell Line; D018679:Cholinergic Agonists / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000150:complications / Q000473:pathology*; D007022:Hypotension / Q000209:etiology / Q000473:pathology*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D010656:Phenylephrine; D010695:Phlorhizin / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D018679:Cholinergic Agonists; D007328:Insulin; D012333:RNA, Messenger; D043585:Receptor, Muscarinic M2; C015688:arecaidine; D010656:Phenylephrine; D001115:Arecoline; D010695:Phlorhizin; D005947:Glucose