Streptozotocin diabetic rats are hypertensive despite reduced hypothalamic responsiveness.

Abstract

SUMMARY To determine whether diabetes predisposes rats to hypertension, tail-cuff systolic pressures were measured in male rats made diabetic by pretreatment with streptozotocin. From Weeks 2 through 7, diabetic rats weighed less but had higher systolic pressures than nondiabetic ones. Further comparisons made while the rats were anesthetized with urethane showed that pressor and sympathetic nerve responses to ventromedial hypothalamic stimulation, as well as pressor responses to injected vasopressin, were significantly reduced in the diabetic group. A generalized reduction of cardiovascular reactivity was considered unlikely because systemic pressor responses to norepinephrine and tyramine were unimpaired. Yet reflex bradycardia elicited by norepinephrine was enhanced indicating that baroreceptor resetting had not occurred. Thus, diabetic rats were characterized by hypertension, narrowed pulse pressure, bradycardia with increased reflex responses to norepinephrine, and reduced pressor responses to hypothalamic stimulation and to vasopressin. The successful induction of diabetes was confirmed not only by the presence of hyperglycemia, hypoinsulinemia, glycosuria, and abnormal glucose tolerance, but also by reductions in pancreatic weight, insulin, and /3-cell content. Although our results suggest that diabetic rats are predisposed to become hypertensive, other mechanisms such as hypothalamic depression may be activated to restrict further elevations in blood pressure. H YPERTENSION is generally believed to be more prevalent among diabetics than nondiabetics, 1 -2 but why this might be so is uncertain. Previous attempts to record blood pressure in rats with experimental diabetes have yielded equivocal results. Although blood pressure in normotensive rats is usually elevated by either alloxan 2 " 1 or streptozotocin, 5 -6 it has also been found unaffected 7 or even slightly decreased by streptozotocin. 8 In spontaneously hypertensive rats (SHR), blood pressure falls during the first few weeks after alloxan diabetes is induced, 4 6 9 but several months later becomes even higher than before. 3 From the Department of Pharmacology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City, Kansas.Supported by Research Grant AM 27660 from the National Institute of Arthritis, Metabolism, and Digestive Diseases.An abstract of this paper was published in Federation Proceedings 40: 391, 1981. Dr. Susumu Sasaku is a postdoctoral research fellow from the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.Address for reprints: Dr. Ruben D. Bunag, Department of Pharmacology, University of Kansas Medical Center, 39th and Rainbow Boulevard, Kansas City, Kansas 66103.Received May 27, 1981; revision accepted December 7, 1981. While trying to characterize the cardiovascular changes occurring in normotensive rats that had been pretreated with streptozotocin, we found the ensuing diabetes accompanied by mild hypertension. Both blood pressure 10 and blood sugar" a...

The effects of endothelin‐1 and NG‐nitro‐l‐arginine methyl ester on regional haemodynamics in conscious rats with streptozotocin‐induced diabetes mellitus

“…However, this cannot be the full explanation of the present findings, since cardiac reflex responses to the pressor effects of vasopressin, angiotensin II or methoxamine are not reduced in STZtreated, Wistar rats (Hebden et al, 1987b). Several studies have reported on resting arterial blood pressure following STZ treatment; some have shown diabetic rats are hypertensive (Kawashima et al, 1978;Bunag et al, 1982;Funakawa et al, 1983), whereas others have found they are normotensive (Rodgers, 1986;Yamamoto, 1988) or hypotensive (Kohler et al, 1980;Hebden et al, 1987a;Kusaka et al, 1987;Tomlinson et al, 1989;1990). The difference between the results from this present study and our earlier studies, in which we reported hypotension in diabetic rats (Hebden et al, 1987a,b;Tomlinson et al, 1989;1990), is that previously both systolic and diastolic blood pressures were recorded, and it was systolic pressure which was consistently reduced (Hebden et al, 1987a;Tomlinson et al, 1989).…”

Insulin reverses hypertension and hypothalamic depression in streptozotocin diabetic rats.

“…Furthermore, electrical stimulation of the ventromedial hypothalamus elicited larger pressor and sympathetic nerve responses from insulin-treated rats than from untreated controls (table 4). Inasmuch as these changes are opposite to those produced during induction of diabetes, 10 our results imply that insulin treatment restores normal cardiovascular and hypothalamic function.…”

“…Plasma vasopressin becomes elevated in diabetic patients as well as hypertensive rats, and upon finding pressor responses to vasopressin reduced in streptozotocin diabetic rats we suggested that reduced responsiveness may be due to receptor saturation. 10 An alternative mechanism based on impaired baroreceptor buffering has been proposed to explain enhancement of pressor responses to vasopressin after intracerebroventricular injection of angiotensin, 29 or in salt-sensitive genetically hypertensive rats. 30 Whatever the cause may be, our finding of larger pressor responses to vasopressin in insulin-treated than in untreated diabetic rats (table 5) supports the conclusion that cardiovascular dysfunction in diabetes can be effectively reversed by insulin.…”

“…10 The present studies were done to determine how the cardiovascular, neural, and hypothalamic changes occurring in streptozotocin-induced diabetes would be affected by insulin treatment.…”

An impedance method for blood pressure measurement in awake rats without preheating.

“…The sensitivity is such that the small but significant difference in SBP between normal and diabetic rats 18 can be easily demonstrated. The designs for recording the differentiated impedance are relatively simple and can be constructed by most electrical engineering laboratories.…”