Insulin-exacerbated hypertension in captopril-treated spontaneously hypertensive rats: role of sympathoexcitation.
Insulin excess exacerbates hypertension in spontaneously hypertensive rats (SHR). This study examined the relative contribution of the renin-angiotensin system and the sympathetic nervous system in this phenomenon. In SHR, daily subcutaneous injections of insulin were initiated either before short-term angiotensin-converting enzyme inhibition with captopril or after lifetime captopril treatment. Insulin treatment resulted in significant increases in mean arterial pressure and heart rate and captopril treatment lowered arterial pressure, but captopril did not lower arterial pressure more in the insulin-treated compared with control rats. To test the contribution of the sympathetic nervous system to this form of hypertension, each rat was intravenously infused with either a ganglionic blocker (i.e., hexamethonium) or a centrally acting alpha2-adrenergic receptor agonist (i.e., clonidine). Administration of either agent largely eliminated the differences in mean arterial pressure and heart rate between the insulin-treated and saline-treated SHR, irrespective of captopril treatment. These data indicate that in SHR, the ability of insulin to increase blood pressure is closely related to sympathoexcitation, which is unresponsive to blockade of angiotensin-converting enzyme.
Roysommuti
Sanya
S
Department of Cell Biology, University of Alabama at Birmingham, 35294-0006, USA.
Mozaffari
Mahmood S
MS
Wyss
J Michael
JM
D000320:Adrenergic Fibers / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D051381:Rats; D011918:Rats, Inbred SHR
D007328:Insulin; D002216:Captopril