Chunlong Huang

The contribution of brain angiotensin II to the baroreflex regulation of renal sympathetic nerve activity in conscious normotensive and hypertensive rats

Angiotensin II receptor density in the brain is elevated when dietary salt intake is raised or in the state of hypertension. The aim of this study was to evaluate whether the angiotensin II modulation of the baroreceptor control of renal sympathetic nerve activity was altered under these conditions. Wistar rats, fed either a regular (0.25% w/w sodium) or high‐salt diet (3.1% w/w sodium), or stroke‐prone spontaneously hypertensive rats (SHRSPs) were implanted with cannulae in the carotid artery, jugular vein and the cerebroventricle and with recording electrodes on the renal sympathetic nerves. Three days later, baroreceptor gain curves were generated for renal sympathetic nerve activity and heart rate before and following intracerebroventricular (i.c.v.) administration of losartan (15 μg) to block angiotensin AT1 receptors. The rats fed a regular diet had a mean blood pressure of 116 ± 3 mmHg and heart rate of 467 ± 25 beats min−1, which remained unchanged after the i.c.v. administration of losartan. The sensitivity or curvature coefficient of the baroreceptor curve for renal sympathetic nerve activity was increased by 36% (P < 0.05) following losartan. In the rats fed a high‐salt diet, all cardiovascular variables and the losartan‐induced increase in the baroreceptor curvature coefficient for renal sympathetic nerve activity (29%) were similar to values in rats on the regular sodium diet. The heart rate baroreceptor curvature coefficient was not altered in either the rats fed a regular or a high‐salt diet. The slope of the renal sympathetic nerve activity baroreflex gain curve in the SHRSPs was less and the increase following administration of losartan (54%) was greater than in the Wistar rats. These data indicate that in the conscious state, the tonic inhibitory action of brain angiotensin II on the baroreflex regulation of renal sympathetic nerve activity was unaffected by raised dietary sodium, but its role was enhanced in the SHRSPs.

A study of the action of angiotensin II on perfusion through the cortex and papilla of the rat kidney

The effect of angiotensin II on blood pressure and perfusion of blood through the cortex and papilla regions of the kidney was determined in pentobarbitone‐anaesthetized rats which were subjected to laser‐Doppler flowmetry to estimate regional renal haemodynamics. Angiotensin II was infused at 10, 45 and 150 ng (kg body weight‐1 min‐1) which caused dose‐related increases in blood pressure of 3, 12 and 24%, respectively, and decreases in cortical perfusion of 9, 15 and 24%, respectively. Papillary perfusion did not change at any dose of angiotensin II. This pattern and magnitude of responses to angiotensin II in blood pressure, cortical and papillary perfusions was essentially unaffected (a) following blockade of cyclo‐oxygenase activity with indomethacin (1.3 mg kg‐1 plus 2 mg kg‐1 h‐1), (b) during infusion of a bradykinin antagonist, at 1.3 micrograms min‐1, (c) when renal perfusion pressure was regulated at control levels and (d) following Methylene Blue administration to inhibit potential endothelial‐derived relaxing factor production. By contrast, infusion of phenylephrine at 5, 10 and 20 micrograms kg‐1 min‐1 caused dose‐related increases in blood pressure and decreases in both cortical and papillary perfusions reaching some 28, 7 and 17% respectively at the highest dose of phenylephrine used. These results showed that both cortex and papilla were sensitive to vasoconstrictor agents. They are compatible with the suggestion that angiotensin II regulates cortical but not papillary perfusion in the kidney, and that these responses do not depend on prostaglandin, bradykinin, renal perfusion pressure or endothelium‐derived relaxing factor.

Neural regulation of kidney function by the somatosensory system in normotensive and hypertensive rats

This investigation examined the renal sympathetic nerve and renal excretory responses to somatosensory stimulation in normotensive and stroke-prone spontaneously hypertensive rats (SHRSP). Somatosensory activation was achieved by either subcutaneous capsaicin administration or exposure of the airways tract to irritant fumes from acetic acid in chloralose-urethan-anesthetized animals. In Wistar rats, blood pressure increased between 10 and 20% (P < 0.001-0.01), renal perfusion pressure was maintained unchanged, renal hemodynamics were unaltered, and urine flow and sodium excretion were decreased by 25 to 50% (P < 0.001-0.05). In the SHRSP, the somatosensory-induced increases in blood pressure were slightly larger (approximately 15-20% P < 0.05) than those of the Wistar rats, whereas the excretory responses were one-half those of the normotensive animals (P < 0.05). The somatosensory challenges reflexly increased integrated renal sympathetic nerve activity in both normotensive and hypertensive rats. The power spectral analysis demonstrated that the increases in percentage power at heart rate frequency and total power were two to three times more (P < 0.05) in the Wistar rats compared with the SHRSP. The reduced ability of the SHRSP to modulate the energy in the renal sympathetic nerve signal at heart rate frequency might explain in part the attenuated functional responses to the somatosensory challenges.This investigation examined the renal sympathetic nerve and renal excretory responses to somatosensory stimulation in normotensive and stroke-prone spontaneously hypertensive rats (SHRSP). Somatosensory activation was achieved by either subcutaneous capsaicin administration or exposure of the airways tract to irritant fumes from acetic acid in chloralose-urethan-anesthetized animals. In Wistar rats, blood pressure increased between 10 and 20% ( P < 0.001-0.01), renal perfusion pressure was maintained unchanged, renal hemodynamics were unaltered, and urine flow and sodium excretion were decreased by 25 to 50% ( P < 0.001-0.05). In the SHRSP, the somatosensory-induced increases in blood pressure were slightly larger (∼15-20% P < 0.05) than those of the Wistar rats, whereas the excretory responses were one-half those of the normotensive animals ( P < 0.05). The somatosensory challenges reflexly increased integrated renal sympathetic nerve activity in both normotensive and hypertensive rats. The power spectral analysis demonstrated that the increases in percentage power at heart rate frequency and total power were two to three times more ( P < 0.05) in the Wistar rats compared with the SHRSP. The reduced ability of the SHRSP to modulate the energy in the renal sympathetic nerve signal at heart rate frequency might explain in part the attenuated functional responses to the somatosensory challenges.

Effect of nitrendipine on autoregulation of perfusion in the cortex and papilla of kidneys from Wistar and stroke prone spontaneously hypertensive rats

1 This investigation examined the autoregulatory efficiency of different vascular regions of the normotensive and stroke prone‐spontaneously hypertensive rat (SP‐SHR) kidney and determined how these myogenic responses were dependent upon extracellular calcium. In acute studies, renal autoregulatory blood perfusion curves for cortex and papilla were generated, autoregulatory indices (AIs) calculated as a ratio of the perfusion change divided by the ratio of the pressure difference where zero represents perfect and 1 equates to no autoregulation. The influence of a calcium channel antagonist on this AI was measured at both cortex and papilla. 2 Rats were anaesthetized with sodium pentobarbitone, the kidney exposed and cortical and papillary perfusion measured by Laser‐Doppler flowmetry. Groups of rats either received no drug or nitrendipine at either 0.125 or 0.25 μg kg−1 min−1. 3 In the Wistar normotensive rats there was efficient autoregulation in the cortex (AI = 0.21 ± 0.17), from 127 to 90 mmHg, but not in the papilla (AI = 0.89 ± 0.08), while below 90 mmHg perfusion in both regions decreased with renal perfusion pressure. Nitrendipine attenuated cortical autoregulation at the higher pressure range (AI = 0.62 ± 0.13 and 0.92 ± 0.10 at the low and high dose, respectively) while having no effect on the papillary pressure perfusion pattern. 4 In the SP‐SHR, reduction in renal perfusion pressure, from 150 to 100 mmHg, gave a cortical AI of 0.49 ± 0.10, indicating impaired autoregulation, whereas the papilla demonstrated little myogenic response. Over the high pressure range in the presence of both doses of nitrendipine there was neither cortical (AI of 0.75 ± 0.11 and 0.94 ± 0.12, respectively) nor papillary autoregulation. 5 Autoregulation in the renal cortex but not papilla of the young Wistar rats is well developed. The myogenic responses are attenuated by the calcium channel antagonists suggesting that they are dependent upon the availability of extracellular calcium. Cortical autoregulation in the SP‐SHR is deficient compared to the normotensive rats and is further impaired by the calcium channel antagonists.

Role of ANG II in mediating somatosensory-induced renal nerve-dependent antinatriuresis in the rat

This study examined the renal nerve-dependent renal hemodynamic and tubular responses to somatosensory stimulation in the anesthetized rat by use of subcutaneously applied capsaicin when the action of ANG II was blocked peripherally or selectively within the brain. Activation of skin somatosensory receptors caused a transient reversible 10-15% increase in blood pressure, and while renal perfusion pressure was regulated at control levels, there was a transient fall in urine flow and sodium excretion even though both renal blood flow and glomerular filtration rate were unchanged. These reflexly induced excretory responses were abolished when the renal nerves were sectioned. Administration of the ANG II AT1-receptor antagonist, losartan, either intravenously at 3 or 10 mg/kg or locally into the lateral cerebroventricles at 15 microg plus 7.5 microg/h, had no effect on capsaicin-induced vasopressor responses but blocked the reductions in urine flow and sodium excretion. These findings are consistent with ANG II being involved in at least two stages in the reflex, one centrally and one at the periphery.

Role of Brain Angiotensin II on Somatosensory-Induced Antinatriuresis in Hypertensive Rats

Abstract—The aim of this investigation was to compare the contribution of brain angiotensin II in mediating the transmission of a somatosensory stimulus within the brain to generate a renal sympathetic nerve-dependent antidiuresis and antinatriuresis in normotensive Wistar rats and stroke-prone spontaneously hypertensive rats (SHRSP). In anesthetized Wistar rats, stimulation of somatosensory receptors by subcutaneous capsaicin increased blood pressure by 9%, had no effect on renal hemodynamics, but decreased urinary flow and sodium excretion by 30% to 40%. These antidiuretic and antinatriuretic, but not blood pressure, responses were absent after intracerebroventricular losartan administration to block angiotensin II type 1 receptors. By contrast, in the SHRSP, although subcutaneous capsaicin raised blood pressure and renal blood flow, neither glomerular filtration rate, urinary flow, nor sodium excretion changed, and this pattern of responses was unaffected after intracerebroventricular losartan. However, an intracerebroventricular infusion of angiotensin II increased basal blood pressure and fluid output, and the capsaicin challenge elicited vasopressor, antidiuretic, and antinatriuretic responses similar in magnitude to those observed in the Wistar rats. The capsaicin challenge in the SHRSP also caused a slowly developing, long-lasting fall in blood pressure and fluid excretion. These findings show that angiotensin II is a necessary component in the somatorenal reflex in normotensive rats but that endogenous angiotensin II is unable to exert this role in SHRSP.

Influence of dietary sodium on the blood pressure and renal sympathetic nerve activity responses to intracerebroventricular angiotensin II and angiotensin III in anaesthetized rats

The regulation of blood pressure and sympathetic outflow by the brain renin–angiotensin system in animals subjected to raised or lowered dietary Na+ intake is unclear. This study compared the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to intracerebroventricular (i.c.v.) infusion of angiotensin II (AngII) and III (AngIII) before and after peripheral V1 receptor blockade (V1B) in α‐chloralose–urethane‐anaesthetized rats fed a low (0.03%, LNa+), normal (0.3%, NNa+) or high Na+ diet (3.0%, HNa+) from 4 to 11 weeks of age. The rise in MAP 2 min post AngII i.c.v. was greater in HNa+ (14 ± 3 mmHg) versus LNa+ (8 ± 1 mmHg, P < 0.05) and after AngIII i.c.v. in HNa+ (14 ± 3 mmHg) versus NNa+ (6 ± 1 mmHg, P < 0.05) and LNa+ (7 ± 1 mmHg, P < 0.05). The MAP responses to AngII and AngIII i.c.v. were abolished after V1B in LNa+, but were only attenuated in HNa+. In NNa+, V1B blunted the MAP responses to AngII and abolished those to AngIII. The MAP remained elevated 30 min after AngII in all groups, but returned to baseline levels 15 min after AngIII in NNa+ and HNa+ (P < 0.01). Twenty minutes after i.c.v. AngII, RSNA rose above baseline in HNa+ (112 ± 1%), a response not observed in the LNa+ and NNa+ groups. Twenty minutes post AngIII i.c.v., RSNA was elevated in both HNa (109 ± 2%) and NNa+ (109 ± 2%). After V1B, RSNA rose only in the HNa+ group 15 min post AngIII infusion (109 ± 1%). Together, these findings: (1) suggest that HNa+ intake augments the MAP and RSNA responses to i.c.v. AngII and AngIII; (2) highlight an important role for peripheral V1 receptors during these responses; and (3) differentiate the effects of AngII and AngIII on blood pressure and RSNA.

Role of brain angiotensin II in the somatosensory induced antinatriuresis in the anaesthetized rat.

1. The present study set out to explore the importance of angiotensin (Ang)II in the brain in allowing the somatosensory system to cause a reflex renal nerve‐mediated reduction in renal sodium and water excretion.

An investigation into the influence of vasopressin on perfusion of the cortex and papilla of the rat kidney

An investigation was undertaken to examine the effects of vasopressin on blood pressure and perfusion of the cortical and papillary regions of the kidney, and to determine the receptor subtype involved. Pentobarbitone‐anaesthetized rats were used and laser‐Doppler flowmetry applied to measure regional renal haemodynamics. Infusion of vasopressin at 10, 20 and 40 mU kg‐1 min‐1 caused dose‐related increases in blood pressure and reductions in cortical and papillary perfusion of approximately 21, 35 and 41%, respectively at the highest dose. Administration of the V1‐receptor antagonist, [1‐(beta‐mercapto‐beta,beta‐cyclopentamethylene propionic acid), 2‐(o‐methyl)tyrosine]‐Arg8‐vasopressin, at 1 microgram kg‐1 plus 5 micrograms kg‐1 h‐1 or four times this dose had no effect on the basal levels of any variable. Vasopressin administration during the low dose of antagonist increased blood pressure and reduced papillary perfusion, the magnitudes of which were only slightly less than those obtained in the absence of the drug, whereas there was a significant attenuation of the response in cortical perfusion. During infusion of the V1 antagonist at 4 micrograms kg‐1 plus 20 micrograms kg‐1 h‐1, vasopressin had no effect on either blood pressure or renal haemodynamics. Infusion of the V2 antagonist, [d(CH2)5, D‐Phe2, Ile4, Arg8, Ala9‐NH2]‐vasopressin at 1 microgram kg‐1 plus 5 micrograms kg‐1 h‐1, and twice this dose had no effect on the basal value of any variable and had no effect on the ability of vasopressin to induce an increase in blood pressure or cause reductions in renal cortical and papillary perfusions. However, the administration of the V2 antagonist at 4 micrograms kg‐1 plus 20 micrograms kg‐1 h‐1 significantly attenuated blood pressure, cortical and papillary perfusion responses to the vasopressin. These studies have shown that vasopressin, given at doses which increased blood pressure, caused dose‐related decreases in perfusion of renal cortex as well as the papilla. The data further show that these systemic and renal actions were mediated primarily by V1‐receptors and that the contribution of V2‐receptors at these vascular beds was very small.

Effect of nitrendipine on renal cortical and papillary autoregulation in hypertensive rats

Renal cortical and papillary perfusions were assessed by laser-Doppler flowmetry and autoregulatory indices. There was cortical autoregulation (autoregulatory index of 0.31 +/- 0.08) in Wistar from 160 to 100 mm Hg, but not in the papilla, which was abolished by nitrendipine, 0.125 and 0.25 micrograms kg-1 min-1. In SHRSP the cortex, but not the papilla, exhibited autoregulation from 180 to 120 mm Hg (autoregulatory index of 0.27 +/- 0.10) but not during low and high doses of nitrendipine. The non-clipped kidney cortex of 2K1C Goldblatt rats autoregulated from 190 to 130 mm Hg (autoregulatory index of 0.20 +/- 0.13), but was inhibited only by the higher dose of nitrendipine. In mature Wistar and SHRSP cortical autoregulation is blocked effectively by nitrendipine whereas the 2K1C Goldblatt hypertensive rats are relatively resistant.