Influence of streptozotocin-induced diabetes on blood pressure and on renin formation and release

Abstract

I.v. injection of 40 mg/kg or 65 mg/kg streptozotocin reliably induced diabetes in female Sprague-Dawley rats, but failed to induced hypertension within the following 42 days. In most animals injected with the higher dose and in some animals injected with the lower dose the tail blood flow was permanently impaired so that no blood pressure signals could be obtained by tail plethysmography. This phenomenon occurred also when the drug was injected into the jugular vein and thus was not due to a local effect of streptozotocin. 15 days after 65 mg/kg streptozotocin, the mean arterial pressure of the rats was similar to that of controls, when measured inthe awake state (carotid cannula) or under ether anaesthesia. 42 days after streptozotocin, under pentobarbital anaesthesia, the blood pressure was again normal in the animals given 40 mg/kg of the drug and depressed in the animals given 65 mg/kg of the drug 42 days previously. The increase of blood pressure induced by 1 microgram/kg (-)-noradrenaline i.v. was similar in the latter group of animals and in controls. The renal cortical renin concentration was much lower than in controls 42 days after either dose of streptozotocin, while the plasma renin activity was normal (40 mg/kg) or increased 65 mg/kg). The low renal renin content may have been due to the diabetic state, rather than to the drug itself. Adrenal medullary dopamine-beta-hydroxylase activity was increased 42 days after the higher dose of streptozotocin.

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).…”

Streptozotocin diabetic rats are hypertensive despite reduced hypothalamic responsiveness.

“…Arguments against derangements of the reninangiotensin system are: 1) the renin-angiotensin system is suppressed in alloxan diabetic rats that become hypertensive; 31 2) plasma renin levels are generally low in diabetic patients, whether normotensive or hypertensive; 32 33 and 3) blood pressure is unaffected in streptozotocin diabetic rats even when plasma renin levels are high. 7 Furthermore, although renal disease is common in clinical diabetes 2 and a glomerulopathy occurs after 6 months in rats treated with high doses (90 mg) of streptozotocin, 34 the kidneys we examined after 8 weeks, though enlarged, were still essentially normal. Notwithstanding these arguments, renal dysfunction cannot be completely ignored because type I (juvenile onset) diabetes, which resembles the streptozotocin diabetic model, is usually associated with sodium-mediated, low-renin hypertension.…”

“…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.…”

Biphasic Alteration of Renin-Angiotensin-Aldosterone System in Streptozotocin-Diabetic Rats

“…However, they did not notice the rise of PR A in acute stage of hyperglycemia. Koh ler et al [6] reported the increase of PR A in STZ-treated rats in chronic state o f hypergly cemia. 42 days after the injection, though the blood sampling for PRA assay was done under anesthetized conditions.…”

“…Alterations in the activity o f renin-angio tensin-aldosterone system have been exten sively studied in human diabetics as well as diabetic animals [1], Most studies have reported the hypofunction o f the system resulting in lowered plasma levels o f renin and aldosterone (PAC) [2][3][4][5], However, other investigators reported rather an increased plasma renin activity (PRA) or angiotensin II (A II) level [6,7], Since the existence of chronic diabetic complications such as neu ropathy [4] and nephropathy [5] may modify the functional state o f renin-angiotensinaldosterone system, the exact impact o f dia betes mellitus itself on this system may be difficult to be assessed in established human diabetics.…”