Production of sustained hypertension by chronic intrarenal norepinephrine infusion in conscious dogs.
The purpose of this study was to determine whether increased sympathetic nervous system activity with proportionally greater stimulation to the kidney could result in sustained hypertension. This was simulated by continuous intrarenal norepinephrine infusion. Effects of chronic infusion of norepinephrine (0.285 microng/kg per min) into the renal artery and inferior vena cava were compared in uniephrectomized conscious dogs. Ten days of intrarenal norepinephrine infusion produced a sustained rise in mean arterial pressure (25 mm Hg), and a 32-mEg positive sodium balance occurred. Inferior vena caval infusion caused a transient rise, lasting 24 hours, in mean arterial pressure which was associated with a 54-mEq natriuresis. With renal artery infusion, peripheral plasma renin activity rose from 1.0 +/- 00.2 to 4.4 +/- 0.8 ng angiotensin I/ml per hour at 1 hour (P less than 0.002) and fell to 1.4 +/- 0.4 at 24 hours (not significant). Inferior vena caval infusion produced a similar result. [Sar1,ala8]angiotensin II (6 MICrong/kg per min) produced no significant change in arterial blood pressure. (alpha-Adrenergic blockade with phentolamine normalized the blood pressure. Renal plasma flow was chronically decreased by about 25% in dogs given intrarenal norepinephrine; no significant change in glomerular filtration rate occurred. The cardiac output decreased from a control of 7.2 +/- 0.6 to 4.8 +/- 0.1 liters/min (P less than 0.01) and total peripheral resistance was increased from a control of 13 +/- 1 to 26 +/- 1 resistance units (RU) (P less than 0.0005) in dogs given intrarenal norepinephrine. The data indicate that chronic intrarenal infusion of norepinephrine in uninephrectomized conscious dogs results in sustained hypertension characterized by decreased renal plasma flow, normal glomerular filtration rate, positive sodium balance, and increased total peripheral resistance due to norepinephrine-dependent vasoconstriction.
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D009318:Natriuresis / Q000187:drug effects; D009638:Norepinephrine / Q000008:administration & dosage* / Q000097:blood; D010646:Phentolamine / Q000008:administration & dosage; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000008:administration & dosage
D000804:Angiotensin II; D000450:Aldosterone; D012083:Renin; D012504:Saralasin; D009638:Norepinephrine; D010646:Phentolamine