Vascular hypersensitivity to noradrenaline: a possible mechanism of hypertension in rats with chronic uraemia.
Studies were performed to evaluate the mechanism involved in the hypertension of moderate renal failure in partially (five-sixth) nephrectomized rats. Cardiac index (CI) was studied by means of the microsphere technique, and systemic vascular resistance (SVR) calculated from the mean arterial resistance MAP/CI, in four groups of experimental animals: (A) partially nephrectomized rats; (B) group A rats chronically treated with the calcium channel blocker verapamil; (C) sham-operated rats; (D) sham-operated rats treated with verapamil. The results demonstrate a significant increase in MAP in group A rats, which was due to a 72% increase in SVR as compared with groups C and D. In group B rats, MAP decreased significantly owing to a marked decrease in SVR (40%) as compared with group A. However, MAP remained higher in group B than in group C. The vascular responsiveness to noradrenaline was studied in group A, group C and group A rats after parathyroidectomy (group A1). An increased pressor responsiveness to noradrenaline was indicated by a shift of the noradrenaline dose-response curve to the left in group A rats as compared with group C rats. This change was corrected after partial nephrectomy. We conclude that hypertension in nephrectomized rats is due to an increase in SVR, and that an increased pressor responsiveness to catecholamines may play a role in this phenomenon. Furthermore, verapamil reduced the hypertension, and parathyroidectomy improved the abnormal sensitivity to noradrenaline in group A rats. These results raise the possibility that an abnormality in calcium metabolism, possibly due to secondary hyperparathyroidism, may be implicated in the hypertension of mildly uraemic rats.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D006977:Hypertension, Renal / Q000209:etiology*; D008297:Male; D009392:Nephrectomy; D009638:Norepinephrine / Q000494:pharmacology*; D010280:Parathyroid Glands / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014511:Uremia / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D014700:Verapamil; D009638:Norepinephrine