Altered responsiveness to sympathetic nerve stimulation and agonists of isolated left atria of diabetic rats: no evidence for involvement of hypothyroidism.
To clarify the role of hypothyroidism in diabetes-induced sympathetic neuropathy, we examined the responsiveness to sympathetic nerve stimulation and to agonists of the left atria of streptozotocin-induced diabetic rats, and compared it with those in hypothyroid, thyroxine(T4)-treated diabetic or T4-treated hypothyroid rats. Positive inotropic response of isolated left atria to transmural nerve stimulation (TNS) was examined in the presence of atropine. In diabetic rats, plasma triiodothyronine and T4 levels decreased markedly. The responses to TNS and norepinephrine (NE) also decreased. The decrease was greater in response to TNS, which may be due to the reduction of presynaptic NE release. As to the postsynaptic response, the maximal response to NE decreased without any significant change in ED50 value, and a similar decrease in the maximal response to Ca++ was also observed in spite of a slight decrease in the beta receptor density. Therefore, in diabetic rats the decreased response to TNS may result mainly from a decreased NE release from nerve endings and a decreased contractility beyond the adrenoceptor level. In hypothyroid rats, the response to TNS and NE decreased, and the decrease was again greater in response to TNS. The decrease in the NE response was due to the increased ED50 value without any change in the maximal response. Similarly, the maximal response to Ca++ did not change. Thus in the hypothyroid rats, the decreased response to TNS probably results from a decreased NE release from nerve endings as well as a decreased sensitivity to NE.(ABSTRACT TRUNCATED AT 250 WORDS)
Sato
N
N
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Hashimoto
H
H
Takiguchi
Y
Y
Nakashima
M
M
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D007037:Hypothyroidism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013963:Thyroid Hormones / Q000097:blood
D013963:Thyroid Hormones; D009638:Norepinephrine