title: Hyperinsulinemic rats are normotensive but sensitized to angiotensin II.
abstract: The effect of insulin on blood pressure (BP) is debated, and an involvement of an activated renin-angiotensin aldosterone system (RAAS) has been suggested. We studied the effect of chronic insulin infusion on telemetry BP and assessed sympathetic activity and dependence of the RAAS. Female Sprague-Dawley rats received insulin (2 units/day, INS group, n = 12) or insulin combined with losartan (30 mg.kg(-1).day(-1), INS+LOS group, n = 10), the angiotensin II receptor antagonist, for 6 wk. Losartan-treated (LOS group, n = 10) and untreated rats served as controls (n = 11). We used telemetry to measure BP and heart rate (HR), and acute ganglion blockade and air-jet stress to investigate possible control of BP by the sympathetic nervous system. In addition, we used myograph technique to study vascular function ex vivo. The INS and INS+LOS groups developed euglycemic hyperinsulinemia. Insulin did not affect BP but increased HR (27 beats/min on average). Ganglion blockade reduced mean arterial pressure (MAP) similarly in all groups. Air-jet stress did not increase sympathetic reactivity but rather revealed possible blunting of the stress response in hyperinsulinemia. Chronic losartan markedly reduced 24-h-MAP in the INS+LOS group (-38 +/- 1 mmHg P < 0.001) compared with the LOS group (-18 +/- 1 mmHg, P <or= 0.05). While insulin did not affect vascular function per se, losartan improved endothelial function in the aorta of insulin-treated rats. Our results raise doubt regarding the role of hyperinsulinemia in hypertension. Moreover, we found no evidence that insulin affects sympathetic nervous system activity. However, chronic losartan treatment revealed an important interaction between insulin and RAAS in BP control.
authors.affiliation: Department of Molecular and Clinical Medicine/Clinical Physiology, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Johansson
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Andersson
authors.forename: Camilla
authors.initials: C
authors.lastname: Alexanderson
authors.forename: Ole
authors.initials: O
authors.lastname: Skøtt
authors.forename: Agneta
authors.initials: A
authors.lastname: Holmäng
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000503:physiopathology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D006946:Hyperinsulinism / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000008:administration & dosage; D007332:Insulin Infusion Systems; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D009213:Myography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D013686:Telemetry; D013997:Time Factors; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001786:Blood Glucose; D005730:Ganglionic Blockers; D007328:Insulin; D014665:Vasodilator Agents; D000804:Angiotensin II; D018738:Hexamethonium; D012083:Renin; D005947:Glucose; D019808:Losartan; D000109:Acetylcholine