Ventricular relaxation of diabetic spontaneously hypertensive rat.

Abstract

Diabetes, and possibly the hypothyroidism that attends diabetes, impairs mechanical relaxation of ventricular muscle, in part by depressing the rate of Ca 2+ uptake by sarcoplasmic reticulum. Left ventricular hypertrophy exacerbates the adverse effects of diabetes on cardiac performance, but its effects on relaxation variables have not been well characterized. We examined the impact of streptozotocin-induced diabetes (8 weeks) on ventricular pressure load-dependent relaxation and sarcoplasmic reticular calcium uptake of hearts from spontaneously hypertensive rats and Wistar-Kyoto rats. Subsets of diabetic hypertensive rats were treated with either insulin (10 units/kg/day) or triiodothyronine (8-10 /tg/kg/day). Diabetes impaired load-dependent relaxation and depressed sarcoplasmic reticular calcium uptake only in spontaneously hypertensive rat hearts. Either insulin or triiodothyronine treatment prevented the diabetes-induced depressions of both mechanical and biochemical indexes of relaxation. The results suggest that 1) hypertrophic ventricles of spontaneously hypertensive rats are more susceptible to the detrimental effects of diabetes on relaxation indexes than are the nonhypertrophic Wistar-Kyoto rat ventricles, and 2) the hypothyroidism that attends diabetes may contribute to the impaired relaxation of diabetic spontaneously hypertensive rat left ventricle. have an impact on ventricular relaxation. The presence of LVH alone may or may not be associated with impaired relaxation. "17 However, when diabetes coexists with LVH in the spontaneously hypertensive rat (SHR), the rate of left ventricular pressure decline of perfused hearts is more profoundly depressed when compared with the effects of diabetes in normotensive rat strains. -13 Isometric relaxation is also prolonged in hypertrophic papillary muscles from the diabetic renovascular hypertensive rat.12 These results would suggest that combined effects of diabetes and LVH on SR Ca 2+ uptake might be more pronounced than the influence of either condition individually. However, the interaction between diabetes and LVH on the relation between myocardial relaxation and SR calcium uptake has not been characterized.Reduced serum levels of thyroid hormones are often associated with diabetes, l *-n and this hypothyroidism (or "low thyroid state") may contribute to diabetic cardiomyopathy. Thyroid hormone deficiencies, like diabetes, can lead to prolonged relaxation and depressed rates of SR calcium uptake in the myocardium. 18- 19 The effects of hypothyroidism on these measurements are well correlated, both in nonhypertrophic and hypertrophic ventricles. 20 Treatment of the diabetic SHR with triiodothyronine (T 3 ) effectively prevents the resultant cardiac dysfunction, 21 -22 but the influence of T 3 treatment in nonhypertensive diabetic rat models is inconsistent.

Differential Responses to Blood Pressure and Oxidative Stress in Streptozotocin-Induced Diabetic Wistar-Kyoto Rats and Spontaneously Hypertensive Rats: Effects of Antioxidant (Honey) Treatment

“…Insulin treatment, in spite of increased serum insulin, also did not reduce hyperglycemia in diabetic SHR [21]. The significantly reduced body weight observed in control SHR is similar to what was reported by other researchers [21]. Our results also showed that in STZ-induced diabetes, the magnitudes of weight loss were more in diabetic SHR than in diabetic WKY.…”

“…This might be due to the severity of hyperglycemia or diabetes in these rats. Insulin treatment, in spite of increased serum insulin, also did not reduce hyperglycemia in diabetic SHR [21]. The significantly reduced body weight observed in control SHR is similar to what was reported by other researchers [21].…”

“…The induction of diabetes in normotensive and hypertensive rats serves as an experimental model to investigate the effects of diabetes alone as well as the combined effects of diabetes and hypertension in rats. In this study, STZ-treated Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) had significantly increased blood glucose levels compared to control WKY and SHR, respectively as previously reported [21]. In our preliminary results, we had observed that resistance to STZ was higher in WKY than in SHR while mortality was much higher in diabetic SHR than in diabetic WKY [22].…”

Impaired cardiac function and IGF-I response in myocytes from calmodulin-diabetic mice: role of Akt and RhoA

“…Characteristics of abnormal function include prolonged duration and reduced rate of contraction and relaxation, as measured in whole hearts (5,13), isolated papillary muscle (20,43), and isolated ventricular myocytes under chemically induced and genetically predisposed diabetes (35,36). Similar to our earlier observations, the present study demonstrated prolonged TPS and Fig.…”

Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

“…Recently, we reported that STZ-induced diabetes mellitus caused reduced SBP in SHR [12]. This hypotensive effect of diabetes on elevated blood pressure was also reported by other authors [22–24]. Besides, our study indicated that short-term (3 weeks) administration of Malaysian tualang honey in STZ-induced diabetic SHR resulted in further reduction in SBP [12].…”