1. Vasoactive substances as regulators of renal growth.
- Author
-
Wolf G
- Subjects
- Angiotensin II physiology, Animals, Arginine Vasopressin physiology, Atrial Natriuretic Factor physiology, Endothelins physiology, Humans, Kidney blood supply, Kidney drug effects, Nitric Oxide physiology, Prostaglandins E physiology, Thromboxane A2 physiology, Vasoconstrictor Agents pharmacology, Vasodilator Agents pharmacology, Kidney growth & development, Vasoconstrictor Agents metabolism, Vasodilator Agents metabolism
- Abstract
The influential studies by Hostetter and associates [103] as well as by others in the last decade have firmly established the association between adaptive increases in renal hemodynamics as well as tubular reabsorption and the progression of renal disease. Many different vasoactive hormones may be involved in such regulatory processes. On the other hand, many investigators have observed that compensatory renal growth, although initially helping to restore functional renal tissue, may be rather harmful in the long-term for renal function, even in the absence of concomitant hemodynamic changes. These apparently separate areas of renal pathophysiology have become united by the identification of the growth regulatory properties of many vasoactive substances. Thus, a perturbation of vasoconstrictors and vasodilatory substances may not only influence vascular tone, glomerular filtration rate and renal plasma flow but also the growth regulation of distinct populations of cells along the nephron. As a generalization, it appears that vasoconstrictors stimulate growth of renal cells (mitogenesis and hypertrophy), whereas vasodilators inhibit the growth response. It can be speculated that similar effects of different hormones may depend on the activation of common second messenger pathway, e.g. the ANG-II-, AVP-, ET-induced mesangial proliferation through the phosphorylation of a common set of target proteins, or the antimitogenic effects of ANP, EDRF and PGE2 through an increase in intracellular cGMP. However, the majority of the growth regulatory effects of vasoactive substances have been studied in relatively artificial cell culture systems. Nevertheless, the well-documented protective effects of ACE inhibitors on renal function in several models include effects on renal growth. The rapid development of new vasoactive drugs like the recently introduced nonpeptide ANG II receptor antagonists may also offer an opportunity to influence renal growth [104]. The mechanisms of the progression of renal disease have become fascinatingly complex, and the next years will most likely witness major achievements in the elucidation of chronic renal pathophysiology on both cellular and molecular levels.
- Published
- 1993