Contractile responses to various stimuli in isolated resistance vessels from simultaneously hypertensive and streptozotocin-diabetic rats.
Diabetes mellitus and hypertension are common chronic diseases that frequently occur simultaneously. The induction of streptozotocin (STZ) diabetes mellitus in spontaneously hypertensive rats (SHR) offers the opportunity to investigate the influence of both entities in a reproducible manner. We investigated the effects of various vasoconstrictors on isolated small arteries from the mesenteric vascular bed of normotensive rats (Wistar-Kyoto rats, WKY) and SHR with chronic (8 weeks), STZ-induced diabetes mellitus. No consistent changes in hemodynamic parameters of the (STZ-) normotensive and (STZ-) hypertensive rats were noted. The K(+)-normalization procedure yields the individual optimal lumen diameter, which was the same for the arteries of the four groups of rats. The passive wall tension resulting from this normalization procedure was higher only in preparations from the control hypertensive group as compared with those from the control normotensive rats. Morphological investigations showed that small arteries from control SHR had an increased tunica media thickness as compared with those of control WKY; the STZ-WKY had an increased tunica media thickness as compared with preparations from control WKY. The vasoconstriction caused by alpha 1-adrenoceptor stimulation [norepinephrine (NE), methoxamine] and serotonin is unchanged in chronic experimental diabetes. The diabetic state reduced the sensitivity [-log EC50(M)] for the concentration-response curves (CRC) of calcium chloride. The CRC of potassium chloride indicated the same sensitivities, but maximal active wall tensions of vessels from STZ-SHR were reduced as compared with those from STZ-WKY. The well-known enhancement of the effects of various contractile stimuli caused by hypertension could not be demonstrated for the isolated small arteries used in the present study, although a nonsignificant tendency was observed. However, the STZ-diabetic state did not cause important additional pharmacodynamic changes, despite the morphological alterations in those vessels.
Kam
K L
KL
Department of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, Netherlands.
Hendriks
M G
MG
Pijl
A J
AJ
van Marle
J
J
van Veen
H A
HA
Pfaffendorf
M
M
van Zwieten
P A
PA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D002122:Calcium Chloride / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013311:Streptozocin; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D001786:Blood Glucose; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D013311:Streptozocin; D011189:Potassium Chloride; D008729:Methoxamine; D002122:Calcium Chloride; D009638:Norepinephrine