Evidence for Renotrophin as a Causal Factor in Renal Hypertension

Abstract

Most of the methods used for the production of experimental renal hypertension involve a reduction in the amount of functional renal tissue. According to the renotrophin hypothesis, the blood pressure of animals with experimental hypertension should be reduced or normalized if the rate of production of renotrophin is reduced (hypophysectomy, thyroidectomy, low protein diet) or if the functional renal mass is increased (kidney transplant, parabiosis). Conversely, the blood pressure should rise to higher levels or hypertension develop if the rate of production of renotrophin is increased (thyroid hormones, somatotrophin, testosterone, thyrotrophin, gonadotrophin in males, protein-rich diets) or if the functional renal mass is further reduced (sensitizing actions of unilateral nephrectomy, etc.). Experimental evidence to be presented conforms with the renotrophin hypothesis and its 4 corollaries.

Humoral Regulation of Renal Growth

“…These include parabiotic, in vivo, and in vitro assays. In general, the three different methodologies support the existence of a renotropic factor (or factors) but further investigations are needed to clarify its precise roles in compensatory renal growth.Remaining viable kidney tissue grows by hypertrophy (cell enlargement) and/or hyperplasia (cell division) [1][2][3][4][5][6] following injury and/or loss of renal mass. Accordingly, survival of the organism may depend on one or both of these processes.…”

“…Likewise, unilateral ureteroperitoneal fistula neither enhances renal DNA synthesis [40] nor mitotic rate [41] in the same manner as unilateral nephrectomy. As a first approximation, it appears that changes in renal mass rather than alterations in renal function trigger compensatory renal growth [22,42,43], In 1958 Braun-Menéndez [1] postulated that a circu lating substance controlled renal growth. He proposed that this humoral regulator, which he called renotropin, played a key role in both renal growth and hypertension.…”

Reversibility of Renal Atrophy Caused by Unilateral Reduction of Renal Blood Supply*

“…The hypothesis which takes into account most of the pertinent observations has been proposed by Braun-Menendez (16). In short, kidney growth is regulated by protein metabolites (renotrophins) which are normally destroyed by the kidney; following reduction in renal mass, they accumulate and stimulate renal growth until a new equilibrium is reached.…”

Partial Characterization of a Renotropic Factor

“…Evi dence favours that a humoral renal growth factor(s), commonly referred to as renotro pin, incites and/or controls compensatory renal growth [2][3][4][5]. The concept of a circu lating renal growth factor is strengthened by the discovery of circulating mitogenic pro teins for various tissues such as epidermis [6], liver [7][8][9] and nerve [10],…”