FRUSEMIDE INHIBITION OF SYMPATHETIC VASOCONSTRICTION IN THE RAT IN SITU BLOOD PERFUSED MESENTERY

Mesenteric perfusion pressure was measured in the in situ blood-perfused mesentery of anaesthetized rats. Increases in perfusion pressure were produced by mesenteric periarterial electrical stimulation at 3, 6 and 10 Hz before and after the administration of frusemide 5 mg/kg intravenously (i.v.) or vehicle. Loss of volume due to diuresis was prevented by replacement with intravenous saline. Frusemide did not cause any changes in blood pressure or baseline perfusion pressure. Responses to electrical stimulation were inhibited by frusemide (P less than 0.05) but unchanged by vehicle administration. Acute bilateral nephrectomy or treatment with indomethacin (2 mg/kg i.v.) prevented the inhibitory effect of frusemide on responses to sympathetic nerve stimulation. Responses to sympathetic nerve stimulation were potentiated by an infusion of angiotensin II (12 ng/min) into the mesenteric artery. This infusion did not alter either blood pressure or baseline perfusion pressure. Administration of frusemide 5 mg/kg i.v. attenuated the potentiating effect of angiotensin II on vasoconstrictor responses to electrical nerve stimulation. Frusemide may lead to the release of a prostanoid or prostanoid precursor which inhibits vascular constrictor responses.     

ENDOTHELIUM-DEPENDENT INHIBITION OF SYMPATHETIC VASOCONSTRICTION BY FRUSEMIDE ADMINISTRATION TO RATS

1. Segments of the tail artery of the rat were cannulated at both ends and mounted in an organ bath filled with Krebs solution. 2. Using an extracorporeal circuit, blood was pumped at a constant 2 ml/min from the carotid artery of anaesthetized rats to perfuse the segment of tail artery, and returned to the donor rat via the jugular vein. 3. Peri-arterial electrical stimulation of the ex vivo blood perfused tail artery at 5 Hz produced vasoconstriction and an increase in perfusion pressure. 4. The intravenous administration of frusemide 5 mg/kg to the donor rat resulted in an inhibition of the vasoconstrictor responses of the perfused tail artery segment. Diuresis-induced losses of volume and frusemide were prevented by a urinary bladder-venous shunt. 5. Removal of the endothelium from the tail artery segment, by perfusion with dry gas for 4 min, prevented the vasoconstrictor-inhibitory effect of frusemide administration. Removal of the endothelium was confirmed histologically and by the absence of a vasodilator response to acetylcholine. 6. On the basis of these and previous results it is concluded that parenteral frusemide administration releases an unidentified but non-prostanoid hormone from the kidney which produces an endothelium-dependent inhibition of sympathetic vascoconstriction.     

ENDOTHELIN-1 ENHANCES VASOCONSTRICTOR RESPONSES TO SYMPATHETIC NERVE STIMULATION AND NORADRENALINE IN THE RABBIT EAR ARTERY

1. In rabbit isolated perfused ear arteries denuded of endothelium, a low concentration of endothelin-1 (0.1 nmol/L) that had no direct vasoconstrictor action produced slowly developing enhancements of vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation. The enhancements reached maximal levels after 60 min of exposure to endothelin-1. 2. A higher concentration of endothelin-1 (1 nmol/L), which produced a slow-developing increase in perfusion pressure of 70 mmHg over the course of 1 h, significantly enhanced vasoconstrictor responses to sympathetic nerve stimulation for the first 30 min, after which there was no significant enhancement. Responses to noradrenaline were not enhanced by 1 nmol/L endothelin-1. 3. The enhancing effect of low concentrations of endothelin-1 on vasoconstrictor responses to sympathetic nerve stimulation and noradrenaline may play a physiological role in modulating vasomotor function.     

EFFECTS OF FIVE NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ON THE RENAL AND SYSTEMIC RESPONSES TO ARACHIDONATE IN CONSCIOUS DOGS

1. The effects of five different non-steroidal anti-inflammatory drugs (NSAID) on the renal blood flow responses to arachidonate were compared. 2. Arachidonate (5-200 micrograms/kg) injected into the renal arteries of conscious dogs caused dose-related renal vasodilatation with no systemic effects. 3. Aspirin (35 mg/kg), phenylbutazone (12 mg/kg) and ibuprofen (25 mg/kg) all markedly reduced arachidonate-induced renal vasodilatation. 4. In contrast, neither indomethacin (3 mg/kg) or its related drug sulindac sulphide (6 mg/kg) significantly reduced arachidonate-induced renal vasodilatation. 5. All NSAID abolished the hypotensive response to intravenous injection of arachidonate (10 mg). 6. Thus, indomethacin and sulindac did not block the effects of renal artery injections of arachidonate but did abolish the systemic effects. Aspirin, phenylbutazone and ibuprofen greatly reduced responses to both renal artery and intravenous arachidonate. 7. Indomethacin and aspirin both reduced the production of prostaglandin E2 and 6-keto-PGF1 alpha by dog renal cortical microsomes in vitro. 8. Thus, indomethacin and sulindac had different effects to other NSAID on arachidonate-induced renal vasodilatation. The results are compatible with the hypothesis that some sites of prostaglandin production in the kidneys of conscious dogs may be relatively resistant to inhibition by indomethacin and sulindac.     

INFLUENCE OF CARDIAC AFFERENTS ON TIME-DEPENDENT CHANGES IN THE RENAL SYMPATHETIC BAROREFLEX OF CONSCIOUS RABBITS

1. The stability of the renal sympathetic baroreflex and nasopharyngeal reflex, and the role of cardiac sensory receptors, was studied in conscious rabbits over a 5 h experimental period. 2. Renal sympathetic nerve activity (SNA) was recorded during (i) slow ramp changes in mean arterial pressure (MAP) of 1-2 mmHg/s induced by inflating perivascular balloon cuffs, and (ii) the inhalation of cigarette smoke. Experiments were repeated in other rabbits after blocking cardiac afferents with 5% intrapericardial procaine. 3. Baroreflex responses to the first two caval cuff inflations of the day were significantly greater than subsequent responses. After this, triplicate sets of reflex curves were relatively stable during a 2 h period in the morning. When the experiment was repeated in the afternoon, there was a significant attenuation of baroreflex range and a small fall in resting renal SNA which were abolished by pericardial procaine. 4. Changes in baroreflex properties were minimal when the reflex was assessed only twice, at the beginning and end of a 5 h period. No change was seen in the nasopharyngeal reflex whether the rabbits had been subjected to few or to many cuff inflations. 5. We conclude that time dependent changes can occur in the renal sympathetic baroreflex of conscious rabbits which must be allowed for by appropriate protocol design. These include increasing inhibitory influences from cardiac sensory receptors in experimental situations requiring multiple reflex estimations.     

EFFECT OF DIETARY SALT LOADING AND HIGH-CALCIUM DIET ON VASCULAR SMOOTH MUSCLE RESPONSES AND ENDOTHELIUM FUNCTION IN RATS

1. The present study examined the effects of concurrent manipulation of dietary calcium and salt on contractile responses of vascular smooth muscle (VSM) and endothelial function of aortic rings from Sprague-Dawley rats. 2. Salt loading enhanced the contractile response of the aortic rings to noradrenaline (NA), an effect that was blunted by a high calciu. intake. 3. Removal of the endothelium and incubation of aortic rings in physiological salt solution containing methylene blue increased the sensitivity of the rings t. NA. 4. The increase in the sensitivity of aortic rings induced by endothelium removal was more pronounced in aortic rings from salt-loade. rats. 5. Acetylcholine caused similar degrees of relaxation in all experimental groups, but the relaxation to histamine was smalle. (P < 0.05) in salt-loaded rats than in other groups of rats; however, after removal of the endothelium, the contractile response to histamine was higher in salt-loaded rats. 6. The results indicate that the hypersensitivity of isolated aortic rings to agonists, as observed in salt-loaded rats, is due to altered responses of the VSM and not as a result of changes in the endothelium. In addition, salt loading tends to increase the synthesis of endothelium-dependent relaxing factor. The ability of salt loading to enhance the contractile responses of VSM to agonists can be prevented by supplementing the diet with high calcium.     

RENAL SYMPATHETIC BAROREFLEX EFFECTS OF ANGIOTENSIN II INFUSIONS INTO THE ROSTRAL VENTROLATERAL MEDULLA OF THE RABBIT

1. The effects of local infusion of angiotensin II (AII) into the rostral ventrolateral medulla (RVLM) pressor area on the renal sympathetic baroreflex were compared with the excitatory amino acid glutamate in urethane anaesthetized rabbits with chronically implanted renal nerve electrodes. Baroreflex blood pressure-renal nerve activity curves were obtained by intravenous infusion of phenylephrine and nitroprusside before and after treatments. 2. Infusion of 4 pmol/min of All into the RVLM increased blood pressure by 12 ± 2 mmHg and transiently increased resting sympathetic nerve activity. The renal sympathetic baroreflex curves were shifted to the right. The upper plateau of the sympathetic reflex increased by 29 ± 8% (n= 6, P < 0.025). 3. Infusions of glutamate into the RVLM, at a dose which was equipressor to that of AII, also increased resting renal sympathetic nerve activity. In contrast to AII, this increase was maintained throughout the infusion. Glutamate shifted the reflex curve to the right and increased the upper plateau of the sympathetic reflex by 44 ± 5% without affecting the lower plateau. 4. These results support the suggestion that AII can act at the level of the RVLM pressor area to facilitate baroreflex control of renal sympathetic activity in a similar fashion to that produced by fourth ventricular administration. 5. Thus the RVLM is a likely candidate site for modulation of the renal sympathetic baroreflex. The similarity of the actions of AII to those of glutamate suggest that it may directly excite sympathetic vasomotor cells in this region.     

DIFFERENTIAL BLOCKADE OF THE RENAL VASOCONSTRICTOR AND DIURETIC RESPONSES TO ENDOTHELIN-1 BY ENDOTHELIN ANTAGONIST

1. The effect of cyclo(d-Trp-d-Asp—Pro-d-Val—Leu) (or BQ123), a selective ETa receptor antagonist, on the vasoconstrictor and diuretic responses elicited by endothelin-1 (ET-1) was examined in conscious sheep with chronic indwelling renal arterial cannulae. 2. Using low dose close renal arterial infusion, ET-1 has potent effects on the kidney causing a marked decrease in effective renal plasma flow and an increase in urine output and free water clearance in the normally hydrated animal. 3. The vasoconstrictor response to renal arterial infusion of ET-1 at 5 μg/h was blunted by renal arterial infusion of the ET_A receptor selective antagonist, BQ123 (400 μg/h). 4. In contrast, the effect of ET-1 on urine production and free water clearance was not affected by this dose of BQ123. 5. The differential effect of BQ123 on renal blood flow and urine production suggests that these effects of endothelin on the kidney are mediated through different receptor mechanisms.     

RENAL RESPONSES TO ANGIOTENSIN II IN CONSCIOUS DOGS: EFFECTS OF ASPIRIN AND INDOMETHACIN

1. Angiotensin II was infused into the renal artery of unanaesthetized dogs at 0.4 and 2.0 ng/kg per min for 40 min each. 2. Indomethacin (3 mg/kg, and 1 mg/kg per h infusion i.v.) accentuated the angiotensin II-induced falls in glomerular filtration rate, renal blood flow and urine flow rate. Indomethacin did not alter the effects of angiotensin II on Na+ or K+ excretions. 3. Aspirin (35 mg/kg p.o. 2.5 h and 0.5 h prior to experiment) did not significantly change the renal effects of angiotensin II. 4. Both aspirin and indomethacin accentuated renal vasoconstriction during briefer (5 min) angiotensin II infusion. 5. Thus indomethacin and aspirin had markedly different effects on the actions of angiotensin II in the kidney. This suggests that at least one of these drugs has actions which affect angiotensin II-mediated vasoconstriction other than via cyclooxygenase inhibition.     

EFFECT OF RENAL AND ADRENAL DENERVATION ON THE RENIN RESPONSE TO SLOW HAEMORRHAGE IN DOGS

SUMMARY 1. The effect on plasma renin activity of moderate slow haemorrhage (7.5 ml. kg⁻¹. h⁻¹ for 2 h) was studied in intact dogs and in dogs whose adrenals and kidneys had been denervated surgically.
2. In dogs with intact renal and adrenal nerves, plasma renin activity rose during haemorrhage without any accompanying change in systemic blood pressure, but with marked decreases in renal function, an increased filtration fraction and an increased haematocrit. The latter effects can be attributed to sympathetic stimulation evoked by haemorrhage.
3. In dogs with denervated kidneys and adrenals, haemorrhage did not result in a significant elevation of plasma renin activity until the 2 h collection period, at which time mean systemic blood pressure had fallen 32 mmHg. Renal function changes were less marked and neither filtration fraction nor haematocrit rose, suggesting the absence of sympathetic stimulation.
4. It concluded that the sympathetic nervous system plays an important role in the renin response to slow haemorrhage until such time as blood pressure falls sufficiently to activate a second stimulatory mechanism, perhaps a renal baro-receptor.     

HAEMODYNAMIC EFFECT OF ENDOTHELIN, A NOVEL POTENT VASOCONSTRICTOR IN DOGS

1. The effects of endothelin (40 and 400 pmol/kg, intravenous (i.v.), a novel vasoconstrictor, on haemodynamics were evaluated in normal dogs and dogs treated with hexamethonium. 2. The lower dose of endothelin caused no significant changes in mean blood pressure (MBP), heart rate (HR), cardiac output (CO), or total peripheral resistance (TPR) in normal dogs. In dogs treated with hexamethonium MBP decreased transiently associated with decrease in TPR. 3. In both dogs, the higher dose of endothelin caused MBP increase with CO increase in an early phase, and with TPR increase in a later phase. In normal dogs, the CO decreased 60 min after endothelin, but in dogs treated with hexamethonium the decrease in CO was not significant. 4. Electrocardiograms showed ST changes and arrhythmias. 5. Thus, endothelin has dual effects on both the vasculature and the heart, its effect depending on its dose and the time after its administration: initial vasodilation followed by prolonged vasoconstriction, and cardiostimulation followed by cardiosuppression. The cardiosuppression appears to be mediated in part by a neural mechanism.     

EFFECT OF ANGIOTENSIN-CONVERTING ENZYME INHIBITION ON RENAL NOREPINEPHRINE SPILLOVER RATE AND BAROREFLEX RESPONSES IN CONSCIOUS RABBITS

1. To evaluate the effects of angiotensin-converting enzyme (ACE) inhibition on sympathetic nerve activity, renal and total norepinephrine (NE) spillover rates were examined under control conditions and during enalaprilat infusion at rest and in response to sodium nitroprusside (SNP)-induced hypotension. 2. Resting renal and total NE spillover rate during enalaprilat infusion were similar to control values. 3. During SNP infusion at 10 μg/kg per min, renal NE spillover rate increased by 26% in enalaprilat-treated group and by 39% in controls, in response to falls in mean arterial pressure (MAP) of 25 and 19% respectively. 4. During sympathetic stimulation induced by SNP, total NE spillover rate was significantly increased in both groups, but the 50% (s.e.m. = 12) increase in the enalaprilat-treated group was less (P<0.05) than the 97% (s.e.m. = 16) change observed in controls. 5. Enalaprilat treatment resulted in a higher renal to total NE spillover ratio (P<0.05). The ratio fell in parallel in both groups during SNP-induced hypotension. 6. This study indicates that the sympathetic nervous system interacts dynamically with the renin-angiotensin system during hypotensive stimulation but this occurs predominantly at sites other than the kidney.     

MODULATION OF VASOCONSTRICTION BY ENDOTHELIUM-DERIVED NITRIC OXIDE: THE INFLUENCE OF VASCULAR DISEASE

1. The endothelium makes a significant contribution to the regulation of vascular tone through the release of potent vasodilator agents such as nitric oxide (NO) and prostacyclin (PGI₂) as well as vasoconstrictor compounds such as endothelin. Recognition of this function of the endothelium has created a new focus for the investigation of vasoconstrictor activity under physiological and pathological conditions. 2. It has been well established that removal of the endothelium enhances responses to a variety of contractile agents in conductance arteries and that such modulation is predominantly due to the release of NO. The use of selective inhibitors of NO synthesis has confirmed that the endothelium-derived nitric oxide also modulates constriction in resistance vessels. 3. In a number of cardiovascular disease states there is impairment of endothelial function. Thus one of the consequences of atherosclerosis, hypertension and ischaemia is a reduction in endothelium-dependent vasodilatation, both at a basal level and in response to endogenous and exogenous stimuli. In addition, enhanced responses to vasoconstrictors have been reported in those disease states. Such observations have led to the attractive hypothesis that enhanced constriction in vascular disease results from attenuate NO-induced dilatation. However, whilst there is some evidence that pathological impairment of endothelial function is accompanied by increased constrictor activity, particularly where serotonergic mechanisms are involved, it is inappropriate to make the general assumption that where disease impairs NO activity there will also be increased sensitivity to all constrictor stimuli.     

STRUCTURAL INFLUENCES ON RESISTANCE IN THE HINDLIMB VASCULAR BED OF THE RENAL HYPERTENSIVE RABBIT

1. The contribution of arteriolar structural change to hindlimb vascular resistance was examined in the renal wrap hypertensive rabbit. 2. Haemodynamic variables were recorded at rest and after maximal vascular dilation using sodium nitroprusside and peripheral autonomic effector blockade. In the same animals at the end of experiments, morphometric measurements of hindlimb muscle arterioles were made. 3. Mean arterial pressure (MAP) and hindlimb vascular resistance were elevated in hypertensive animals compared with normotensive animals at rest and after maximal dilation. 4. Lumen area and lumen diameter were reduced whereas wall area and wall area to lumen area ratio were increased in hypertensive animals compared with normotensive animals. 5. In the renal wrap model of hypertension, the reduction in lumen area of arterioles, < 200 pm in diameter, is sufficient to explain the increase in haemodynamic resistance.     

ENDOTHELIN-1 AND THE REGULATION OF VASCULAR TONE

1. In 1988, Yanagisawa et al. reported the presence of a potent peptide from the supernatant of porcine endothelial cells. This was later named endothelin-1 (ET-1) and was found to belong to a new family of vasoconstrictor peptides. There are at least three isoforms of endothelin: ET-1, endothelin-2 and endothelin-3. 2. ET-1 is produced from a larger precursor molecule by endothelin converting enzyme (ECE); there may be a number of ECE but the most physiologically relevant appears to be a membrane-bound neutral metalloprotease. The endothelin precursor is produced on demand and is regulated at the mRNA level. 3. Two subtypes of mammalian endothelin receptors have been cloned and sequenced: ETa receptors which mediate vasoconstriction and ETe receptors which mediate both vasoconstriction and vasodilatation. However, functional studies have indicated that other subtypes of endothelin receptors may exist. 4. ET-1 has a wide range of biological actions apart from its direct effects on vascular tone, including constriction of non-vascular smooth muscle, cardiac effects, mitogenesis and stimulation of the release of hormones such as atrial natriuretic peptide and prostacyclin. At low concentrations which have no direct vasoconstrictor action, ET-1 potentiates the effect of other vasoconstrictor agonists. 5. The precise role of ET-1 in health and disease is not well defined at present; however, there are indications that it may have a role in the pathogenesis of some cardiovascular disease states, including subarachnoid haemorrhage, renal ischaemia and certain types of hypertension.     

THE EFFECTS OF MECLOFENAMATE ON RENAL AND PERIPHERAL VASCULAR BEDS IN CONSCIOUS RABBITS

1. Meclofenamate caused a dose-dependent increase in renovascular resistance in conscious rabbits. 2. This effect was greatest in inner cortical zones at the highest dose (6 mg/kg) but at the lowest dose (0-75 mg/kg) vascular resistance in the outer cortex was preferentially increased. 3. In contrast, meclofenamate increased cerebral perfusion and the proportion of cardiac output received by the testis. No effect was demonstrated on other organs studied. 4. The results suggest a local vasodilator influence of renal prostaglandins in normal conscious rabbits.     

EFFECT OF PURE EICOSAPENTAENOIC ACID FEEDING ON BLOOD PRESSURE AND VASCULAR REACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS

1. This study examined the effects of eicosapentaenoic acid (EPA) treatment on vascular reactivity and blood pressure in spontaneously hypertensive rats (SHR). 2. Twenty SHR were given pure EPA as the methyl ester (280 mg/kg) by gavage for 10 days. An equal number of control rats received vehicle alone. EPA treatment had no effect on blood pressure compared with control rats. 3. Aortic rings from EPA-treated rats, precontracted with PGF2 alpha showed increased endothelium-dependent relaxations to acetylcholine. Endothelium-independent relaxations to sodium nitroprusside were not altered. Rings from rats fed pure EPA did not show any differences in vasoconstrictor responses to noradrenaline or serotonin. 4. Serum thromboxane B2 (TXB2) levels fell 17% in animals given pure EPA, but prostacyclin production was not affected. These responses are less than those seen following Max EPA fish oil. 5. Thus, pure EPA treatment did not lower blood pressure, but may have a direct effect on aortic endothelia and cause increased endothelium-dependent relaxations in response to acetylcholine in SHR.     

EFFECT OF LONG-TERM ADMINISTRATION OF TESTOSTERONE OENANTHATE ON SYMPATHETIC NEUROTRANSMISSION TO RAT ISOLATED SEMINAL VESICLES

1. The effects of prolonged administration of testosterone oenanthate (TE) on sympathetic neurotransmission to the rat isolated seminal vesicle were examined. 2. TE was administered at either 1.2 or 2.4 mg/kg subcutaneously (s.c.) thrice weekly for 8 weeks. A separate group of rats was administered the vehicle, sesame oil, 0.5 mL/kg, s.c. at the same regime and used as controls. TE administration increased plasma testosterone and dihydrotestosterone levels and seminal vesicle weights. TE 2.4 mg/kg suppressed fertility in male rats. 3. The mean -log EC50 values of adrenalin and noradrenaline in seminal vesicles from the control group were 5.30 (95% confidence limits: 5.14, 5.58; d.f. = 14) and 4.92 (95% confidence limits: 4.56, 5.49; d.f. = 14) respectively. Neither of these estimates were modified by TE administration. 4. The mean noradrenaline content (microgram/tissue) in seminal vesicles from control rats was 0.88 +/- 0.09 microgram/tissue. This did not change with TE treatment. Tissue noradrenaline concentration (microgram/g tissue), on the other hand, decreased by more than 50% in preparations from rats treated with TE. This was paralleled by a decrease in the density of catecholamine fluorescence. 5. Mean responses to field stimulation (20 pulses, 60 V dial setting, 2 ms, 1-70 Hz) appeared to decrease in preparations from TE treated groups; this decrease was, however, not statistically significant (P greater than 0.05; d.f. = 15). 6. It is concluded that prolonged administration of testosterone oenanthate to rats, at doses sufficient to suppress fertility, decreases the density of sympathetic innervation to the seminal vesicle by increasing smooth muscle mass. Treatment does not, however, modify the responses of this preparation to exogenously added catecholamines.     

RENAL SYMPATHETIC AND HEART RATE BAROREFLEX FUNCTION IN CONSCIOUS AND ISOFLURANE ANAESTHETIZED NORMOTENSIVE AND CHRONICALLY HYPERTENSIVE RABBITS

1. Baroreflex control of heart rate (HR) has been studied in normotensive (NT) and hypertensive (HT) awake and anaesthetized animals and man, but baroreflex control of sympathetic nerve activity has not been well studied. We investigated baroreflex control of HR and renal sympathetic nerve activity (RSNA) over a wide range of arterial pressure (AP) in conscious and isoflurane (ISO) anaesthetized NT and HT rabbits. 2. Animals were instrumented to record AP, HR and RSNA. Hypertension was accomplished by renal encapsulation. AP-HR and AP-RSNA baroreflex function curves were obtained while awake and after 1.0, 1.5, 2.0 and 2.5% ISO. All baroreflex curves were fit to sigmoid or exponential functions. 3. In conscious rabbits, HT for 3–5 weeks, AP was significantly higher (75.6 ± 0.8 vs 102.3 ± 8.9 mmHg); HR significantly lower (218.0 ± 5.5 vs 189.5 ± 5.5 beats/min); and RSNA not different than NT rabbits (14.9 ± 2.2 vs 9.9 ± 3.2% max RSNA). 4. ISO shifted AP-HR and AP-RSNA baroreflex curves to the left in NT and HT animals, and significantly attenuated baroreflex range and slope. At low ISO concentrations, baroreflex compensation for decreases in AP is limited to small increases in HR and sympathetic nerve activity. At higher ISO concentrations, baroreflex responses to decreases in AP are lost. RSNA responses to increases in AP are preserved with increasing ISO concentrations while HR responses are progressively attenuated. The sole effect of chronic hypertension was to shift the AP-HR and AP-RSNA barocurves to the right along the pressure axis in both conscious and ISO anaesthetized animals with no additional change in range or slope. 5. At this stage of hypertension development, ISO anaesthesia affects baroreflex function equally in normotensive and hypertensive rabbits.