Blood pressure fluctuates continuously throughout life and autoregulation is the primary mechanism that isolates the kidney from this fluctuation. Compared with Wistar rats, Brown Norway (B-N) rats display impaired renal myogenic autoregulation when blood pressure fluctuation is increased. They also are very susceptible to hypertension-induced renal injury. Because blockade of nitric oxide augments myogenic autoregulation in Wistar rats, we compared the response of the myogenic system in B-N rats to nitric oxide blockade with that of other strains [Wistar, Sprague-Dawley, Long-Evans, spontaneously hypertensive (SHR)]. Renal blood flow dynamics were assessed in isoflurane anesthetized rats before and after inhibition of nitric oxide synthase by Lomega-nitro-arginine methyl-ester (L-NAME, 10 mg/kg, iv). Under control conditions, myogenic autoregulation in the B-N rats was weaker than in the other strains. Myogenic autoregulation was not augmented after L-NAME administration in the SHR, but was augmented in all the normotensive rats. The enhancement was significantly greater in B-N rats so that after L-NAME the efficiency of autoregulation did not differ among the strains. The data suggest that nitric oxide is involved in the impaired myogenic autoregulation seen in B-N rats. Furthermore, the similarity of response in Wistar, Long-Evans, and Sprague-Dawley rats suggests that modulation by nitric oxide is a fundamental property of renal myogenic autoregulation.

Animals↗

PubMed2000

Baroreceptors, alpha1-adrenergic receptors, and regulation of mesenteric blood flow.

In the mesenteric circulation of the rat a myogenic autoregulatory system operates at 0.1-0.15 Hz. Negative admittance phase in the region above 0.2 Hz suggested operation of an arterial baroreflex. The present study was designed to test this interpretation and to identify the neurotransmitter involved. In rats anesthetized with isoflurane, blood pressure and mesenteric blood flow (transit time ultrasound) were measured with central mechanisms intact, after sinoaortic denervation, and after denervation of the mesenteric bed. Sinoaortic denervation abrogated the negative phase in the band from 0.3 to 0.6 Hz and increased admittance gain in this region. Subsequent mesenteric denervation had no further effect on the pressure-flow transfer function. In a separate experiment, alpha1-adrenergic blockade reduced, but did not remove, the negative admittance phase in the 0.2- to 0.5-Hz band without altering admittance gain. It is concluded that the baroreflex acting on the mesenteric circulation can be identified by admittance phase, but that admittance gain is uninformative. Part of the response is mediated by alpha1-adrenergic transmission.

Animals↗

PubMed2000

Impaired myogenic autoregulation in kidneys of Brown Norway rats.

The Brown Norway (BN) rat is normotensive and has an extended lifespan but is extremely sensitive to hypertension-induced renal injury. Relative impairment of autoregulation has been implicated in the progression of renal failure whereas absence of myogenic autoregulation is associated with early renal failure. Therefore, we tested the hypothesis that there is conditional failure of renal autoregulation in BN rats. In isoflurane-anesthetized BN rats, the pressure-flow transfer function was normal when pressure fluctuated spontaneously. External forcing increased pressure fluctuation and exposed weakness of the myogenic component of autoregulation; the component mediated by tubuloglomerular feedback was less affected. In the presence of vasopressin to raise renal perfusion pressure, myogenic autoregulation was further impaired during forcing in BN rats but not in Wistar rats. Compensation by the myogenic system was rapidly restored on cessation of forcing, suggesting a functional limitation rather than a structural failure. Graded forcing in Wistar rats and in spontaneously hypertensive rats revealed that compensation due to the myogenic system was strong and independent of forcing amplitude. In contrast, graded forcing in BN rats showed that compensation was reduced when fluctuation of blood pressure was increased but that the reduction was independent of forcing amplitude. The results demonstrate conditional failure of myogenic autoregulation in BN rats. These acute studies provide a possible explanation for the observed sensitivity to hypertension-induced renal injury in BN rats.

Animals↗

PubMed1999

Incommensurate frequencies of major vascular regulatory mechanisms.

The dynamic relationship among three major vascular control mechanisms that operate on large fractions of cardiac output: arterial baroreflex and renal and mesenteric autoregulation, was investigated in conscious rats. Wistar and spontaneously hypertensive rats were studied in their home cages 10 days after implantation of pulsed Doppler flow probes. There was an oscillation of blood pressure centered at 0.45 Hz that is associated with operation of arterial baroreflexes. Hindquarters blood flow displayed a featureless, "1/f' power spectrum, in which no autoregulatory or baroreflex signatures could be discerned, although active control of resistance over a wide range of frequencies was evident. The renal pressure - flow transfer function was dominated by an autoregulatory mechanism with a resonance peak at 0.25 +/- 0.01 Hz. In the mesenteric circulation an autoregulatory mechanism was seen with a resonance peak at 0.15 +/- 0.01 Hz and another active mechanism was seen above 0.2 Hz that appeared from its negative admittance phase to be a baroreflex. The center frequencies of mesenteric and renal autoregulation and of the arterial baroreflex were related in a ratio of 1 : 1.7 +/- 0.1 : 3.0 +/- 0.2 (approximately 4:7:12). Such relatively high order ratios can be expected to minimize the possibility of phase locking and (or) entrainment among the various control mechanisms.

Animals↗

PubMed1999

Nitric oxide, atrial natriuretic factor, and dynamic renal autoregulation.

Inhibition of nitric oxide (NO) synthase by N(omega)-nitro-L-arginine methyl ester (L-NAME) increases arterial pressure (PA) and profoundly reduces renal blood flow (RBF). Here we report that L-NAME causes changes in the PA-RBF transfer function which suggest augmentation of the approximately 0.2 Hz autoregulatory mechanism. Attenuation of PA fluctuations from 0.06 to 0.11 Hz was enhanced, indicating increased efficacy of autoregulation. Also, the rate of gain reduction between 0.1 and 0.2 Hz increased while the associated phase peak became > or = pi/2 radians, indicating emergence of a substantial rate-sensitive component in this system so that autoregulatory responses to rapid PA changes become more vigorous. Infusion of L-arginine partly reversed the pressor response to L-NAME, but not the renal vasoconstriction or the changes in the transfer function. The ability of atrial natriuretic factor (ANF), which also acts via cGMP, to replace NO was assessed. ANF dose dependently reversed but did not prevent the pressor response to L-NAME, indicating additive responses. ANF did not restore RBF or reverse the changes in the transfer function induced by L-NAME. The rate-sensitive component that was enhanced by L-NAME remained prominent, suggesting that either ANF did not adequately replace cGMP or provision of a basal level of cGMP was not able to replace cGMP generated in response to NO. It is concluded that NO synthase inhibition changes RBF dynamics with the most notable change being increased contribution by a rate-sensitive component of the myogenic system.

Animals↗

PubMed1998

Responses of mesenteric and renal blood flow dynamics to acute denervation in anesthetized rats.

Previous studies have shown that renal autoregulation dynamically stabilizes renal blood flow (RBF). The role of renal nerves, particularly of a baroreflex component, in dynamic regulation of RBF remains unclear. The relative roles of autoregulation and mesenteric nerves in dynamic regulation of blood flow in the superior mesenteric artery (MBF) are similarly unclear. In this study, transfer function analysis was used to identify autoregulatory and baroreflex components in the dynamic regulation of RBF and MBF in Wistar rats and young spontaneously hypertensive rats (SHR) anesthetized with isoflurane or halothane. Wistar rats showed effective dynamic autoregulation of both MBF and RBF, as did SHR. Autoregulation was faster in the kidney (0.22 +/- 0.01 Hz) than in the gut (0.13 +/- 0.01 Hz). In the mesenteric, but not the renal bed, the admittance phase was significantly negative between 0.25 and 0. 7 Hz, and the negative phase was abrogated by mesenteric denervation, indicating the presence of an arterial baroreflex. The baroreflex was faster than autoregulation in either bed. The presence of sympathetic effects unrelated to blood pressure was inferred in both vascular beds and appeared to be stronger in the SHR than in the Wistar rats. It is concluded that a physiologically significant baroreflex operates on the mesenteric, but not the renal circulation and that blood flow in both beds is effectively stabilized by autoregulation.

Animals↗

PubMed1998

Dynamic autoregulation in the in vitro perfused hydronephrotic rat kidney.

Renal autoregulation is mediated by tubuloglomerular feedback, operating at 0.03-0.05 Hz, and a faster system, operating at 0.1-0.2 Hz, that has been attributed by exclusion to myogenic vasoconstriction. In this study, we examined dynamic autoregulation in the hydronephrotic rat kidney, which lacks tubuloglomerular feedback but exhibits pressure-induced afferent arteriolar vasoconstriction. Kidneys were harvested under anesthesia from Sprague-Dawley rats and perfused in vitro using defined, colloid-free medium. Renal perfusate flow was assessed during forced pressure fluctuations at mean pressures of 60-140 mmHg. Transfer function analysis revealed passive behavior at 60 mmHg and active, pressure-dependent responses at higher pressures. In all cases, coherence was high (0.89 +/- 0.03 between 0.01 and 0.9 Hz). There was a resonance peak in admittance gain at approximately 0.3 Hz and an associated broad peak in phase angle. Below this frequency, gain declined progressively. The minimum gain achieved at 0.01-0.05 Hz was pressure sensitive, being 1.08 +/- 0.02 at 60 mmHg and 0.71 +/- 0.04 at 140 mmHg. These findings are consistent with in vivo results and with model-based predictions of the dynamics of myogenic autoregulation, supporting the postulate that the rapid component of autoregulation reflects operation of a myogenic mechanism.

Animals↗

PubMed1996

Spontaneous blood pressure fluctuations and renal blood flow dynamics.

Two mechanisms operating at 0.03-0.05 and 0.1-0.2 Hz are involved in autoregulation of renal blood flow (RBF). To examine the behavior of the faster system, the response of RBF to spontaneous fluctuations of arterial pressure was assessed in Sprague-Dawley rats anesthetized by isoflurane or halothane. During halothane anesthesia, autonomous oscillation of total RBF was observed at 0.10-0.15 Hz, and normalized admittance gain became negative at 0.11 +/- 0.01 Hz. During isoflurane anesthesia, there was autonomous power in blood flow in a broad peak between 0.15 and 0.25 Hz, and gain became negative at 0.15 +/- 0.01 Hz. Increasing inspired isoflurane concentration from 1.4 +/- 0.1% to 2.2 +/- 0.1% reduced pressure by 22 +/- 2 mmHg but did not alter blood flow or the transfer function, indicating that the operating frequency was not changed. In another experiment, changing from isoflurane to halothane increased peak power in the autonomous blood flow oscillation fivefold and reduced its frequency from 0.18 +/- 0.01 to 0.14 +/- 0.01 Hz. Gain became negative at a higher frequency (0.16 +/- 0.01 Hz) during isoflurane than halothane anesthesia (0.12 +/- 0.01 Hz). The results show that the 0.1-0.2 Hz system is reliably detected under unforced conditions and provides modest attenuation of pressure fluctuations at < or = 0.1 Hz. Its operating frequency under isoflurane anesthesia is consistent with previous estimates from barbiturate-anesthetized rats, whereas it operates significantly slower under halothane anesthesia.

Administration, Inhalation↗

PubMed1996

Pharmacological modulation of spontaneous renal blood flow dynamics.

Two mechanisms contribute to renal autoregulation. The faster system, which is thought to be myogenic, operates at 0.1-0.2 Hz (i.e., 5-10 s/cycle), while the slower one, tubuloglomerular feedback, operates at 0.03-0.05 Hz (i.e., 20-30 s/cycle). Both attenuate spontaneous or induced fluctuations of blood pressure, but it has proven difficult to separate their individual contributions because there is potential for interaction between the two. The present study was designed to examine the dynamics of the faster system during pharmacological blockade of tubuloglomerular feedback. Normotensive and hypertensive rats were studied under isoflurane or halothane anesthesia. Administration of the loop diuretic furosemide plus the angiotensin II (ANGII) AT1 receptor antagonist losartan caused a 10-fold or greater natriuresis, indicating profound inhibition of ascending limb salt transport, and also produced characteristic changes in the transfer function relating blood pressure (input) to renal blood flow (output). Operation of the 0.1-0.2 Hz mechanism was essentially unaltered, as shown by the presence of a peak in phase angle at 0.1-0.2 Hz and reduction of gain at frequencies slower than 0.15 Hz. The 0.03-0.05 Hz mechanism was markedly inhibited, as shown by loss of the second phase angle peak at 0.03-0.05 Hz, loss of the local maximum in gain at 0.05 Hz, and loss of the second gain reduction below 0.05 Hz. Both during control and after inhibition of tubuloglomerular feedback, the 0.1-0.2 Hz system attenuated = 50% of the effects of spontaneous blood pressure fluctuations, suggesting that this mechanism, operating alone, can significantly stabilize renal blood flow in the face of spontaneous fluctuations of blood pressure.

Anesthetics, Inhalation↗

PubMed1994

In vitro response of rat renal artery to perfusion pressure.

Both tubuloglomerular feedback and a myogenic response contribute to autoregulation of renal blood flow. Vascular interaction initiated by tubuloglomerular feedback has been described and prevents definition, in vivo, of the contribution of myogenic responses to autoregulation. Segments of rat renal artery were perfused in vitro at constant flow while upstream and downstream pressures were measured on-line, allowing determination of resistance. Transmural pressure was governed by a downstream resistor. Outside diameter was measured by an ocular micrometer. The segments were bathed in bicarbonate Ringer solution and perfused with Ringer containing 50 g/L bovine serum albumin. Potassium depolarization reduced the diameter and made it more sensitive to perfusion pressure. Serosal norepinephrine, 10(-7)-10(-5) M, caused graded constriction and increased the axial pressure drop due to vessel resistance. Addition to the perfusate of rat red blood cells to hematocrit approximately 33% significantly reduced arterial diameter and enhanced the increased axial pressure drop induced by 10(-6) M norepinephrine. Sequential elevation of perfusion pressure from 50 to 100 mmHg (1 mmHg = 133.3 Pa) increased the diameter significantly. Red cells reduced the slope of the diameter-pressure relationship. In another experiment, norepinephrine reduced the slope of diameter versus perfusion pressure, while 10(-4) M papaverine plus norepinephrine increased the slope, compared with norepinephrine alone. Norepinephrine caused a sizable axial pressure drop (15.7 +/- 3.7 mmHg), which decayed as perfusion pressure increased; the decay was accentuated by papaverine. The changes in axial pressure drop were linearly related to the inverse 4th power of diameter, indicating that both measurements assessed the same behavior. Several different maneuvers thus affect the relationship between arterial diameter and perfusion pressure, and the relationship between axial pressure drop and perfusion pressure. The results indicate the presence of a myogenic response, which is, however, not strong enough to defend vessel diameter when pressure rises.

Animals↗

PubMed1994

Alpha 2-adrenergic mediation of the effects of angiotensin II on rat renal artery in vitro.

Angiotensin II (ANG II) is a major influence on renal blood flow, acting directly on the renal vasculature and upon other controllers. In vivo observations suggest that ANG II affects renal artery resistance, although explicit in vitro studies have produced negative results. To resolve this issue, potential interactive effects of ANG II on renal artery in vitro were tested. Renal arteries were harvested from ketamine-anesthetized Sprague-Dawley rats and perfused in vitro at constant flow. Resistance was determined from the axial pressure drop while downstream pressure was held constant at approximately 80 mmHg (1 mmHg = 133.3 Pa). ANG II, per se, had only a trivial effect on arterial diameter (-5.5 +/- 1.5% at 10(-7) M ANG II) and failed to affect resistance at concentrations ranging from 10(-11) to 10(-7) M. Norepinephrine caused strong concentration-dependent constriction, increasing resistance from 0.32 +/- 0.04 to 1.86 +/- 0.73 mmHg.mL-1.min at 10(-6) M and 3.27 +/- 0.88 mmHg.mL-1.min at 10(-5) M. In the presence of 10(-8) M ANG II, these responses were significantly increased to 3.31 +/- 1.00 and 5.02 +/- 1.22 mmHg.mL-1.min, respectively. Similarly, in the presence of 10(-6) M norepinephrine, ANG II caused significant, concentration-dependent constriction of renal artery. In a separate experiment, 10(-7) M yohimbine, a relatively specific antagonist of alpha 2-adrenergic receptors, reversed the resistance increment due to ANG II, but not that due to norepinephrine. When yohimbine was applied before norepinephrine and ANG II, it did not affect the response to norepinephrine, but again blocked potentiation of the response by ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1994

Atrial natriuretic factor, angiotensin II, and the slow component of renal autoregulation.

Autoregulation of renal blood flow is highly efficient and is mediated partly by tubuloglomerular feedback (TGF), which couples regulation of blood flow to that of sodium excretion. Atrial natriuretic factor (ANF) dilates preglomerular resistance vessels, in which autoregulation occurs, and has been reported to inhibit TGF. This study addressed potential actions of ANF on the slow, TGF-mediated, component of autoregulation. Renal blood flow was measured by an electromagnetic flow probe in Sprague-Dawley rats anesthetized by halothane or isoflurane while renal perfusion pressure was manipulated by a servo-controlled clamp placed on the aorta between the renal arteries. Progressive reduction of perfusion pressure to 60 mmHg (1 mmHg = 133.3 Pa) induced resetting of autoregulation to operate at the reduced pressure and to defend lower renal blood flow. Infusion of ANF at a dose shown to reliably increase sodium excretion did not affect autoregulation or its resetting. Because resetting is angiotensin II dependent, the converting enzyme inhibitor Enalaprilat was used to provide angiotensin II blockade. As expected, autoregulation did not reset to operate at reduced perfusion pressure. Again ANF was without effect. In a third experiment, relaxation of resistance was assessed in response to repeated steps of perfusion pressure between 65 and 75 mmHg. Time constants of constriction and dilatation were recovered by fitting to a single exponential before and during ANF infusion. Time constants ranged form 0.045 to 0.055 Hz, were consistent with operation of TGF, were not different for constriction or dilatation, and were unaltered by ANF; nor did ANF affect the magnitude of constriction or dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1993

Angiotensin II conditions the slow component of autoregulation of renal blood flow.

Release of a suprarenal aortic clamp results in angiotensin-dependent, arterial pressure-mediated renal vasoconstriction. The experiments reported here were designed to show whether this represents operation of autoregulation and whether the slow component of autoregulation is affected by angiotensin II (ANG II). They were performed using halothane-anesthetized Sprague-Dawley rats. In the 1st experiment renal perfusion pressure (RPP) was reduced in steps from spontaneous level to 45 mmHg and then returned in steps to the spontaneous level. The autoregulatory plateau was left-shifted some 20-30 mmHg, with the lower limit of autoregulation reduced from approximately 85 mmHg on the downward leg to approximately 60 mmHg on the upward leg. This resetting was blocked by captopril. Two experiments examined low pressure autoregulation in more detail. After RPP was reduced, three pairs of steps between 65 and 75 mmHg were performed. Significant renal vasodilatation was observed after downward pressure steps in both experiments. Time constants (tau) of resistance adjustment were recovered from most steps by curve fitting. In both experiments tau down = 0.07 +/- 0.01 Hz was faster than tau up = 0.04 +/- 0.01 Hz. Blockade of ANG II by enalaprilat or by the AT1-receptor blocker losartan potassium significantly inhibited regulatory vasodilatation and vasoconstriction at low RPP. Also, tau down = 0.04 +/- 0.01 Hz collapsed to the value of tau up = 0.04 +/- 0.01 Hz. These results demonstrate a significant role for ANG II in renal autoregulation. They show that ANG II is necessary for autoregulation to reset to operate at reduced arterial pressure and to defend a lower blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗