The kidney plays a crucial role in the long-term control of blood pressure. Many forms of hypertension are characterized by abnormally high renal vascular resistance. Although other vascular beds exhibit elevated resistance, the increase in renal vascular resistance seems to be important in order for blood pressure to remain elevated. Among various renal vascular segments, the afferent and efferent arterioles (Af- and Ef-Art) are thought to not only account for most of the resistance but also comprise the crucial segments that control glomerular hemodynamics and thus excretory function of the kidneys. However, for technical reasons, little is known about the reactivity of these small vessels (10-20 mum in luminal diameter) or their alteration in hypertension. We have recently established an in vitro preparation in which a single microdissected rat Af-Art with its glomerulus is microperfused with and without simultaneous cannulation of the Ef-Art. This preparation has the advantage of allowing us to control both flow and pressure independently by adjusting Ef-Art resistance and measuring pressure in the Af-Art with a fine glass pipette (2 mum, tip diameter) inserted through the perfusion pipette. Furthermore, we are able to observe arteriolar responses directly in the absence of systemic hemodynamic or hormonal influences. We have observed that the Af- Art of the spontaneously hypertensive rat (SHR) exhibits both exaggerated contractile response to increased perfusion pressure and impaired acetylcholine-induced vasodilation as compared to its normotensive control. Using this preparation, we propose to test the hypothesis that locally produced vasoactive substances, such as endothelium-derived relaxing and contracting factors (EDRF and EDCF) and prostaglandins (PGs), are important regulators of the basal tone and vascular reactivity of the glomerular Af- and Ef-Art; and that imbalance between locally produced vasodilators and vasoconstrictors is involved in altered reactivity of the Af- and Ef-Art in hypertension. We will study arteriolar responses to various perfusion pressures, vasoconstrictors and dilators in the presence and absence of pharmacological interventions that alter EDRF, EDCF and/or PGs. Thus our study will clarify the role of paracrine/autocrine hormones in the control of Af- and Ef-Art dynamics in normal and hypertension. The new information we obtain will help us understand the mechanism by which renal vascular resistance is elevated in hypertension and therefore the renal pathophysiology of hypertension.
Showing the most recent 10 out of 381 publications
