Abstract
The present study investigated the influence of chronic hyperinsulinemia on vascular responsiveness induced by adrenergic nerves and calcitonin gene–related peptide–containing (CGRPergic) nerves in pithed rats with insulin resistance. Male Wistar rats (6 weeks old) received 15% fructose solution in drinking fluid for 10 weeks (fructose-drinking rats: FDR), which resulted in significant increases in plasma levels of insulin, total cholesterol and triglyceride, and systolic blood pressure, as compared with control rats. Pithed FDR showed greater adrenergic nerve–mediated pressor response to spinal cord stimulation (SCS) at the lower thoracic vertebra (Th 9–12) and pressor response to exogenous noradrenaline than control rats. In pithed FDR with blood pressure artificially increased by continuous infusion of methoxamine and blockade of autonomic ganglia by hexamethonium, CGRPergic nerve–mediated depressor responses to SCS were significantly smaller than those in control rats, but depressor responses to other vasodilators such as acetylcholine, CGRP and sodium nitroprusside were similar to those in control rats. These results suggest that chronic hyperinsulinemia in FDR facilitates adrenergic nerve–mediated vasoconstriction, which is associated with attenuated CGRPergic nerve–mediated vasodilation.
Similar content being viewed by others
Article PDF
References
Modan M, Halkin H, Almog S, et al: Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. J Clin Invest 1985; 75: 809–817.
Chiristlieb AR, Krolewski AS, Warram JH, Soeldener JS : Is insulin the link between hypertension and obesity? Hypertension 1985; 7 ( Suppl II): II-54–II-57.
Defronzo RA : The effect of insulin on renal sodium metabolism: a review with clinical implications. Diabetologia 1981; 21: 165–171.
Landsberg L : Diet, obesity and hypertension: a hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med 1986; 236: 1081–1090.
Reaven GM, Hoffman BB : A role for insulin in the aetiology and course of hypertension. Lancet 1987; 2: 435–436.
Lembo G, Napoli R, Capaldo B, et al: Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension. J Clin Invest 1992; 90: 24–29.
Hsueh WA, Law RE : Insulin signaling in the arterial wall. Am J Cardiol 1999; 84: 21J–24J.
Marigliano A, Tedde R, Sechi LA, Pala A, Pisanu G, Pacifico A : Insulinemia and blood pressure. Relationships in patients with primary and secondary hypertension, and with or without glucose metabolism impairment. Am J Hypertens 1990; 3: 521–526.
Ferrannini E, Natali A, Capaldo B, Lehtovirt M, Jacob S, Yki-Jarvinen H : Insulin resistance, hyperinsulinemia, and blood pressure. Hypertension 1997; 30: 1144–1149.
Pollare T, Lithell H, Berne C : Insulin resistance is a characteristic feature of primary hypertension independent of obesity. Metabolism 1990; 39: 167–174.
Creager MA, Liang CS, Coffman JD : Beta adrenergic–mediated vasodilator response to insulin in the human forearm. J Pharmacol Exp Ther 1985; 21: 165–171.
Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD : Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994; 94: 1172–1179.
Takatori S, Mizote M, Zamami Y, Kurosaki Y, Kawasaki H : Effects of insulin on vascular responses to spinal cord stimulation and vasoactive agents in pithed rats. Br J Pharmacol 2003; 140: 1137–1145.
Suzuki M, Nomura C, Odaka H, Ikeda H : Effect of an insulin sensitizer, pioglitazone, on hypertension in fructose-drinking rats. Jpn J Pharmacol 1997; 74: 297–302.
Tobey TA, Mondon CE, Zavaroni I, Reaven GM : Mechanism of insulin resistance in fructose-fed rats. Metabolism 1982; 31: 608–612.
Taguchi T, Kawasaki H, Imamura T, Takasaki K : Endogenous calcitonin gene–related peptide mediates nonadrenergic noncholinergic depressor response to spinal cord stimulation in the pithed rat. Circ Res 1992; 71: 357–364.
Kawasaki H, Nuki Y, Yamaga N, Kurosaki Y, Taguchi T : Decreased depressor response mediated by calcitonin gene–related peptide (CGRP)−containing vasodilator nerves to spinal cord stimulation and levels of CGRP mRNA of the dorsal root ganglia in spontaneously hypertensive rats. Hypertens Res 2000; 23: 693–699.
Nuki Y, Kawasaki H, Taguchi T, Takasaki K, Wada A : Effects of dorsal rhizotomy on depressor response to spinal cord stimulation mediated by endogenous calcitonin gene–related peptide in the pithed rat. J Neurosurg 1993; 79: 899–904.
Kawasaki H, Takasaki K, Saito A, Goto K : Calcitonin gene–related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of rat. Nature 1988; 335: 164–167.
Kawasaki H, Nuki C, Saito A, Takasaki K : Role of calcitonin gene–related peptide–containing nerves in the vascular adrenergic neurotransmission. J Pharmacol Exp Ther 1990; 252: 403–409.
Kawasaki H, Inaizumi K, Nakamura A, Hobara N, Kurosaki Y : Chronic angiotensin II inhibition increases levels of calcitonin gene–related peptide mRNA of the dorsal root ganglia in spontaneously hypertensive rats. Hypertens Res 2003; 26: 257–263.
Hobara N, Gessei-Tsutsumi N, Goda M, et al: Long-term inhibition of angiotensin prevents reduction of periarterial innervation of calcitonin gene–related peptide (CGRP)−containing nerves in spontaneously hypertensive rats. Hypertens Res 2005; 28: 465–474.
Regalia J, Cai F, Helke C : Streptozotocin-induced diabetes and the neurochemistry of vagal afferent neurons. Brain Res 2002; 938: 7–14.
Adeghate E : Distribution of calcitonin-gene–related peptide, neuropeptide-Y, vasoactive intestinal polypeptide, cholecystokinin-8, substance P and islet peptides in the pancreas of normal and diabetic rats. Neuropeptides 1999; 33: 227–235.
Okada K, Hirano T, Ran J, Adachi M : Olmesartan medoxomil, an angiotensin II receptor blocker ameliorates insulin resistance and decreases triglyceride production in fructose-fed rats. Hypertens Res; 27: 293–299.
Erdos B, Snipes JA, Miller AW, Busija DW : Cerebrovascular dysfunction in Zucker obese rats is mediated by oxidative stress and protein kinase C. Diabetes 2004; 53: 1352–1359.
Karagiannis J, Reid JJ, Darby I, Roche P, Rand MJ, Li CG : Impaired nitric oxide function in the basilar artery of the obese Zucker rat. J Cardiovasc Pharmacol 2003; 42: 497–505.
Miller AW, Hoenig ME, Ujhelyi MR : Mechanisms of impaired endothelial function associated with insulin resistance. J Cardiovasc Pharmacol Ther 1998; 3: 125–134.
Verma S, Bhanot S, Yao L, Mcneill JH : Defective endothelium–dependent relaxation in fructose-hypertensive rats. Am J Hypertens 1996; 9: 370–376.
De Jongh RT, Serne EH, Ijzerman RG, De Vries G, Stehouwer CD : Impaired microvascular function in obesity: implications for obesity-associated microangiopathy, hypertension, and insulin resistance. Circulation 2004; 109: 2529–2535.
Lteif A, Mather K : Insulin resistance, metabolic syndrome and vascular diseases: update on mechanistic linkages. Can J Cardiol 2004; 20 ( Suppl B): 66B–76B.
Hasegawa K, Yoshida H, Ura N, Murakami H, Hagiwara M, Shimamoto K : The role of renal natriuretic and depressor systems in insulin-resistant hypertensive rats. Hypertens Res 2004; 27: 501–508.
Borst BE : The role of TNF-alpha in insulin resistance. Endocrine 2004; 23: 177–182.
Chen XD, Lei T, Xia T, Gan L, Yang ZQ : Increased expression of resistin and tumor necrosis factor-alpha in pig adipose tissue as well as effect of feeding treatment on resistin and cAMP pathway. Diabetes Obes Metab 2004; 6: 271–279.
Scheen AJ : Pathophysiology of type 2 diabetes. Acta Clin Belg 2003; 58: 335–341.
Iwashima Y, Katsuya T, Ishikawa K, et al: Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension 2004; 43: 1318–1323.
Yamauchi T, Kamon J, Ito Y, et al: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 12: 762–769.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Takatori, S., Zamami, Y., Mio, M. et al. Chronic Hyperinsulinemia Enhances Adrenergic Vasoconstriction and Decreases Calcitonin Gene–Related Peptide–Containing Nerve–Mediated Vasodilation in Pithed Rats. Hypertens Res 29, 361–368 (2006). https://doi.org/10.1291/hypres.29.361
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.29.361
Keywords
This article is cited by
-
Asiatic acid attenuates renin-angiotensin system activation and improves vascular function in high-carbohydrate, high-fat diet fed rats
BMC Complementary and Alternative Medicine (2016)
-
Decreased perivascular CGRP-containing nerves in Otsuka Long–Evans Tokushima Fatty rats with insulin resistance and hypertension
Hypertension Research (2014)
-
Hyperinsulinemia induces hypertension associated with neurogenic vascular dysfunction resulting from abnormal perivascular innervations in rat mesenteric resistance arteries
Hypertension Research (2011)
-
Evidence for the role of α1A-adrenoceptor subtype in the control of renal haemodynamics in fructose-fed Sprague–Dawley rat
European Journal of Nutrition (2011)
-
Pioglitazone opposes neurogenic vascular dysfunction associated with chronic hyperinsulinaemia
British Journal of Pharmacology (2008)