Pharmacological manipulation of alpha- and beta-adrenoceptors in the isolated perfused rat kidney, effects on renal vascular resistance and renin secretion rate

Renin was first described in 1898 by Tigerstedt and Bergmann. It is a proteolytic enzyme involved in the renin -angiotensin system which plays an important role in blood pressure regulation. Several factors are recognized which may influence renin secretion. These factors are renal perfusion pressure, sodium concentration at the macula, densa, renal sympathetic nerve activity, alterations in extracellular sodium concentration and volume, and various humoral factors (hormones, prostaglandines etc.). Because of the complex interrelation between these factors difficulties are encountered when one attempts to clarify the interrelation between vasoactivity, sympathetic nerve activity and renin secretion. This is reflected in the literature where considerable controversy remains on which adrenoceptor subtypes are involved in renin secretion. In addition, interactions between the adrenoceptor subtypes and other receptors have been demonstrated. Because of the complexity of these interrelations we carried out experiments in the isolated perfused rat kidney since in such a model several of the aforementioned factors may be controlled. The main issue of our investigation is which subtype of adrenoceptor could be responsible for the final adjustment in renin secretion. The questions related to this issue are as follows: 1. which adrenoceptors can be defined in the isolated rat kidney by pharmacological methods. 2. which roles can be ascribed to the respective adrenoceptor subtypes in terms of vasoregulation. 3. which adrenoceptors are involved in renin secretion. 4. to what extent are the effects of these adrenoceptors with respect to vasoregulation and renin secretion interdependent. In the next three chapters the renin-angiotensin system, adrenoceptors in general and in the kidney, and methods will be described