Malignant hypertensive crisis induced by chronic intrarenal norepinephrine infusion.
The purpose of the present study was to develop a controllable experimental model in the dog that would consistently and predictably produce a malignant hypertensive crisis, and to determine the sequential changes in renal function, salt and water balance, and hormones that are involved in the transition from benign to accelerated hypertension. Norepinephrine (NE) was infused continuously into the renal artery of unilaterally nephrectomized dogs that were maintained on 50 mEq sodium/day. The infusion rate of NE was increased each day according to the following schedule: 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 microgram/kg/min. During the first 4 to 5 days of intrarenal NE infusion, there was a progressive decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), and increases in plasma renin activity (PRA), mean arterial pressure (MAP), and filtration fraction. At the end of this period of benign hypertension, MAP had risen from a control value of 91 +/- 4 to 132 +/- 8 mm Hg, in association with approximately a 10-fold increase in PRA and a 40% reduction in renal function. Then, suddenly, during the subsequent 24-hour infusion period, the MAP increased abruptly in all animals (MAP = 156 +/- 8 mm Hg), and a hypertensive crisis occurred. This crisis was associated with the following: salt and water depletion, hyponatremia, hypovolemia and hemoconcentration, polydipsia, marked activation of the renin-angiotensin-aldosterone system, increased plasma cortisol concentration, hemolysis, marked impairment in renal function, lethargy, and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D004285:Dogs; D006400:Hematocrit; D006854:Hydrocortisone / Q000097:blood; D006974:Hypertension, Malignant / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D007263:Infusions, Parenteral; D007668:Kidney / Q000473:pathology*; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage*; D011188:Potassium / Q000378:metabolism; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism
D000450:Aldosterone; D012964:Sodium; D012083:Renin; D011188:Potassium; D006854:Hydrocortisone; D009638:Norepinephrine