Enhanced vascular tone in the renal vasculature of spontaneously hypertensive rats.

Abstract

The renal microvascular responses of Wistar-Kyoto and spontaneously hypertensive rats to changes in perfusion pressure were compared using a juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. In the spontaneously hypertensive rats, the internal diameters of arcuate and interlobular arteries and the proximal and distal afferent arterioles averaged 307±26, 52±2, 24±0.9, and 22±1.2 ftm, respectively, at 80 mm Hg. They were 18-35% smaller (p<0.05) than the corresponding vessels measured in Wistar-Kyoto rats. In low calcium media, the arcuate and interlobular arteries and the proximal and distal afferent arterioles of spontaneously hypertensive rats exhibited a greater dilation than the vessels of Wistar-Kyoto rats. These observations suggest that the diameters of the preglomerular vasculature of the spontaneously hypertensive rats are reduced because of an elevated vascular tone rather than structural changes narrowing the lumen of these vessels. These results suggest that enhanced vascular tone in the preglomerular vasculature of juxtamedullary nephrons may contribute to the elevated renal medullary vascular resistance and resetting of the pressure-natriuretic relation previously observed in spontaneously hypertensive rats. (Hypertension 1990;16:648-654) R enal transplantation studies have indicated that some form of renal dysfunction underlies the development of genetic hypertension.12 Nevertheless, the factors that contribute to the "resetting of the kidney in hypertension" remain unknown. Numerous differences in renal function of spontaneously hypertensive rats (SHR) and WistarKyoto (WKY) rats have been described; these include an elevated renal vascular resistance, 3 -5 enhanced renal vascular reactivity to vasoconstrictors, 4 -5 enhanced tubuloglomerular feedback response, 6 and structural changes that increase the wall-to-lumen ratio in the renal vasculature.78 Because most of these changes have been identified in the established phase of hypertension, it remains unclear whether these changes are a cause or a consequence of the disease.We recently reported that the pressure-natriuretic response is blunted in SHR and Dahl salt-sensitive rats before the development of hypertension. 910 In the SHR, the abnormality in the pressure-natriuretic response is associated with a reduction in papillary blood flow 11 and renal interstitial hydrostatic pressure. 12 These observations suggest that an elevation in renal medullary vascular resistance may participate in the resetting of the renal function toward higher pressures in SHR. 11The factors responsible for reducing papillary blood flow in SHR are unknown. Medullary blood flow is derived exclusively from the perfusion of deep nephrons. Thus, structural changes that narrow the lumen of the preglomerular vasculature of juxtamedullary nephrons or alterations in the reactivity of these vessels could be responsible for the!, reduction of papillary blood flow in SHR. The recent development of the in ...

Sympathetic Regulation of the Renal Functions in Rats Reciprocally Congenic for Chromosome 1 Blood Pressure Quantitative Trait Locus

“…Further, the aggravated renal vasoconstriction is suggested to be a key pathomechanism for the development of hypertension in SHR (31,32) and SHRSP (33). Consistent with these reports, the RVR was greater in SHRSP and SHRSPwch1.0, both of which were phenotypically hypertensive, than in WKYpch1.0 and WKY.…”

Antihypertensive effect of mechanism-based inhibition of renal arachidonic acid ω-hydroxylase activity

“…A sim-ilar pattern was also found with ABT and in earlier studies with the heme oxygenase inducer stannous chloride (29,42). During the period when blood pressure rises rapidly in the SHR (5-9 wk of age), 20-HETE formation in renal microsomes is elevated relative to age-matched WKY rats (27,37), and there is a decreased diameter of interlobular and afferent arterioles that can be reversed by blockade of renal 20-HETE formation (12,15,19). The elevation of medullary vascular resistance associated with decreased papillary blood flow contributes to an upward shift of the pressure-natriuresis relationship in the early developmental phase of hypertension in SHRs, and 20-HETE has been implicated in this response (40).…”

“…An increased formation of 20-HETE in the SHR kidney relative to age-matched normotensive WKY rats has been associated with increased renal interlobular and afferent arteriolar resistance (12,15,19). On the other hand, the natriuretic and diuretic effects of 20-HETE would oppose the vascular effects of this eicosanoid and are considered antihypertensive (3,30,38).…”

Impaired Ca 2+ Signaling Attenuates P2X Receptor–Mediated Vasoconstriction of Afferent Arterioles in Angiotensin II Hypertension

“…Although autoregulatory behavior is maintained or exaggerated in certain types of animal hypertension models such as spontaneously hypertensive rats, autoregulatory capability becomes impaired in models of angiotensin II (Ang II)-dependent hypertension. [1][2][3][4][5] Impairment of afferent arteriolar autoregulatory behavior appears to involve a change in vascular smooth muscle calcium signaling. 6 -9 Elevation of cytosolic calcium concentration represents an important component in the afferent arteriolar response to perfusion pressure changes, and pressure-mediated vasoconstriction of afferent arterioles relies heavily on the influx of extracellular calcium through voltage-gated calcium channels.…”