Altered myogenic responsiveness of the renal microvasculature in experimental hypertension

Recent investigations have delineated the renal microvascular responsiveness to pressure, by using isolated afferent arterioles, juxtamedullary nephrons, and isolated perfused hydronephrotic kidneys. Both afferent arterioles and interlobular arteries (ILA) manifest pressure-dependent vasoconstrictor responses to elevated renal arterial pressure. Several recent studies have indicated that the afferent arteriole adjacent to the glomerulus constricts primarily in response to tubuloglomerular feedback signals, whereas the afferent arteriole near the ILA is under the dominant influence of myogenic tone. Furthermore, the responsiveness of the ILA to pressure is dependent on the basal diameter, with the smaller diameter (distal) segments demonstrating more marked responses than do the larger (proximal) segments. The myogenic afferent arteriolar response is shifted to higher perfusion pressure in spontaneously hypertensive rat (SHR) kidneys, and blunted both in Dahl salt-sensitive rats and in Goldblatt renal hypertensive rats. This altered responsiveness of the afferent arteriole may account for the alterations in renal blood flow autoregulation, namely, resetting toward higher pressures in SHR, and impairment in Dahl salt-sensitive rats and Goldblatt hypertensive rats Distal ILA segments vasoconstricted similarly in response to pressure both in SHR and in Wistar-Kyoto rats (WKY), whereas proximal ILA segments did not exhibit vasoconstriction in either strain. The intermediate ILA segment from SHR kidneys manifests more prominent myogenic vasoconstriction than does that from WKY rat kidneys. The enhanced myogenic responsiveness of the intermediate ILA segment may act in concert with afferent arteriolar vasoconstriction to prevent glomerular hypertension in superficial nephrons. Finally, the myogenic vasoconstriction of renal microvessels is mediated in part by voltage-dependent calcium channels, and the altered myogenic response may be associated with modified activity of voltage-dependent calcium channels. Thus, the myogenic preglomerular tone constitutes a pivotal determinant of renal autoregulation, and teleologically may also play an important role in protecting glomeruli from barotrauma in hypertension, whereas the functional myogenic element is soon reinforced by an element of "structural autoregulation' of preglomerular resistance vessels.