Search

The effect of the cyclooxygenase inhibitor indomethacin (3.4 mg/kg/24 hr) on systolic blood pressure (PB) and plasma-renin-activity (PRA) was evaluated in normotensive and renovascular hypertensive rats receiving either a normal or low salt diet. Indomethacin reduced PRA in normal and hypertensive animals on both low and normal salt intake. Indomethacin furthermore, decreased BP in animals on low sodium diet but increased PB in sodium repleted rats. These data suggest that the effect of indomethacin on rat BP may depend on the state of extracellular volume and PRA.

Histological, ultrastructural, immunohistochemical, intravital microscopic and electrophysiological techniques have been applied to study experimental hydronephrosis in rats in order to assess its value as a preparation for the investigation of renal microcirculation and of the electrophysiological properties of the renin-containing juxtaglomerular (JG) cells of the afferent glomerular arteriole. As hydronephrosis develops, the kidney parenchyma becomes progressively thinner owing to tubular atrophy. Twelve weeks after ureteral ligature, this process results in a transparent tissue sheet of about 150-200 microns in thickness. In this preparation, the renal arterial tree as well as the glomeruli can be easily visualized for intravital microscopic studies, e.g. the determination of kidney vessel diameters, or the identification of JG cells for penetration with an intracellular microelectrode. In contrast to the tubular atrophy, the vascular system is well preserved, and the JG cells and the sympathetic axon terminals are ultrastructurally intact. This is also true for the glomeruli, except for a certain confluence of the podocyte foot processes and a thickening of the basal laminae. Renin immunostaining and kidney renin content in the hydronephrotic organ correspond to those in control kidneys. In addition, there are no differences in the plasma renin levels of hydronephrotic and control rats. Intravital microscopic observations reveal that the renal vascular tree reacts in a typical, concentration dependent manner to the vasoconstrictor agent angiotensin II, mainly at the level of the resistance vessels. Electrophysiological recordings from juxtaglomerular granulated cells show a high membrane potential (-60 mV), and spontaneous depolarizing junction potentials, owing to random transmitter release from the nerve terminals. Angiotensin II, an inhibitor of renin release, depolarizes JG cells reversibly. Hence, we may infer that the hydronephrotic rat kidney is a suitable model for in vivo studies of the renal microcirculation as well as for in vitro investigations of the electrophysiological properties of the media cells of the afferent glomerular arteriole.

Experimental hydronephrosis in mice has been studied with histological, ultrastructural, immunohistochemical, biochemical, and electrophysiological techniques to establish its value as a preparation for the investigation of glomerular microcirculation as well as the electrophysiological and biochemical properties of the renin-containing juxtaglomerular (JG) and vascular smooth muscle (VSM) cells of the afferent glomerular arteriole. During developing hydronephrosis the kidney parenchyma becomes progressively thinner as a result of tubular atrophy, being, after 12 weeks, a tissue sheet of about 200 micron in thickness. In this preparation, the renal arterial tree, in particular the glomerular arterioles, and also the glomeruli can be easily visualized. This permits intravital microscopic studies or direct visual identification of JG and VSM cells for microelectrode impalement. In spite of complete tubular atrophy, the vascular system is well preserved. Ultrastructurally, JG and VSM cells as well as the axon terminals innervating the vessels are intact. The same holds for the glomeruli except for a certain confluence of the podocyte foot processes and a thickening of the basal lamina. Renin immunostaining and kidney renin content in the hydronephrotic organ correspond to those in control kidneys. In addition, renin release from this preparation can be stimulated in a typical manner by isoproterenol and inhibited by angiotensin II, indicating that the receptors controling renin release and the secretory mechanism itself are still intact. Electrophysiological recordings from JG and VSM cells show a high membrane potential (-75 mv), and spontaneous depolarizing junction potentials, owing to transmitter release from the nerve terminals. Inhibitors of renin secretion, e.g. angiotensin II, depolarize both cell types, whereas stimulators such as isoproterenol do not change the membrane potential. We conclude that the hydronephrotic mouse kidney is a suitable model for in vitro studies of the electrophysiology and biochemistry of the media cells of the afferent arteriole, as well as for in vivo studies of glomerular microcirculation.