Sustained Reductions In Arterial Pressure Research Articles

PS-BPC06-5: EXOGENOUS THYROXINE INCREASES GLUT4 TRANSLOCATION IN MEMBRANE AND IMPROVES CARDIAC METABOLISM INDEPENDENT OF REDUCED SBP IN INSULIN RESISTANT OLETF RATS

Objective: During insulin resistance the heart undergoes a metabolic shift where fatty acids (FA) account for about 99% of the ATP production, indicative of impaired glucose metabolism. This results in increased reactive oxygen species and lipotoxicity leading to impaired mitochondrial function. Thyroid disorders such as hyperthyroidism and hypothyroidism both have the potential to lead to hypertension. Thyroid hormones (TH) may improve glucose intolerance by increasing glucose reabsorption and metabolism and therefore improve cardiac function and lower the risk of developing hypertension. However, incongruent data exists showing that TH promote oxidative stress and cardiac hypertrophy. Thus, the beneficial effects of TH in the heart during insulin resistance remains controversial. The glucose transport protein, GLUT4, is a downstream target of the TH response element indicating a possible mechanism by which TH regulate glucose metabolism. Design: Insulin resistant, Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the effects of exogenous thyroxine (T4) on glucose metabolism in cardiac tissue. Rats were assigned to four groups: 1) lean, Long Evans Tokushima Otsuka (LETO; n = 6), 2) LETO + T4 (8 μg/100 g BM/d × 5 wks; n = 7), 3) untreated OLETF (n = 6), and 4) OLETF + T4 (n = 7). T4 was administered via osmotic minipumps implanted subcutaneously. Systolic blood pressure (SBP) was measured weekly in conscious rats by tail-cuff plethysmography. Animals were provided water and food ad libitum. Results: SBP increased by 15% in OLETF compared to lean LETO (138 ± 2 vs. 117 ± 1 mm Hg), but T4 did not alter SBP is OLETF strain. T4 increased GLUT4 gene expression by 85% and GLUT4 protein translocation to the membrane by 328% in OLETF. Additionally, T4 increased phosphofructokinase-1, the rate limiting step in glycolysis, by 98% and decreased CD36 gene expression for FA transport by 20% in OLETF. We expect our recent metabolomics and lipidomics data to help better explain these molecular changes. Conclusions: Five-week dose of exogenous T4 did not reduce SBP is OLETF. The results suggest that increased T4 has the potential to increase glucose reabsorption and metabolism in the heart of insulin resistant rats and restore impaired substrate metabolism, but these improvements in substrate metabolism do not translate to sustained reduction in arterial pressure.

Skeletal Muscle Hyperemia: A Potential Bridge Between Post-exercise Hypotension and Glucose Regulation.

For both healthy individuals and patients with type 2 diabetes (T2D), the hemodynamic response to regular physical activity is important for regulating blood glucose, protecting vascular function, and reducing the risk of cardiovascular disease. In addition to these benefits of regular physical activity, evidence suggests even a single bout of dynamic exercise promotes increased insulin-mediated glucose uptake and insulin sensitivity during the acute recovery period. Importantly, post-exercise hypotension (PEH), which is defined as a sustained reduction in arterial pressure following a single bout of exercise, appears to be blunted in those with T2D compared to their non-diabetic counterparts. In this short review, we describe research that suggests the sustained post-exercise vasodilation often observed in PEH may sub-serve glycemic regulation following exercise in both healthy individuals and those with T2D. Furthermore, we discuss the interplay of enhanced perfusion, both macrovascular and microvascular, and glucose flux following exercise. Finally, we propose future research directions to enhance our understanding of the relationship between post-exercise hemodynamics and glucose regulation in healthy individuals and in those with T2D.

Catheter-Based Renal Nerve Ablation as a Novel Hypertension Therapy: Lost, and Then Found, in Translation.

The hypothesis that renal nerves mediate, at least in part, the pathogenesis and maintenance of hypertension is based on decades of preclinical studies and, to a certain extent, recent clinical trials of catheter-based renal nerve ablation (CBRNA) in humans. The first 2 clinical trials for CBRNA, Symplicity HTN-1 and Symplicity HTN-2, reported sustained reductions in arterial pressure in patients with drug-resistant hypertension and set the stage for the first blinded US trial, Symplicity HTN-3. However, Symplicity HTN-3 failed to reach its 6-month efficacy end point, thus jeopardizing the clinical application of CBRNA in the United States. The goal of this article is to reexamine the feasibility of CBRNA to treat hypertension. Preclinical studies on the role of renal nerves in hypertension have been extensively reviewed,1,2 as have the Symplicity HTN-1, 2, and 3 trials.3–7 Therefore, we will review these topics only briefly to provide context for the primary purpose of this article which is to answer the following question: is the outcome of Symplicity HTN-3 because of the failure to translate preclinical knowledge to the clinic, or is our basic understanding of the mechanisms by which renal nerves contribute to hypertension flawed? The kidney is innervated by sympathetic efferent fibers that modulate 3 pharmacological targets for the treatment of hypertension: renin release, tubular sodium reabsorption, and renal vascular resistance.1,2 Although conventional pharmacological treatments of these targets lower arterial pressure, patients often present with negative side effects which may lead to drug incompliance. One rationale for CBRNA is that this treatment would suppress renin release, tubular sodium reabsorption, and renal vasoconstriction, while avoiding the side effects associated with more globally acting pharmacotherapies. The kidney is also innervated by renal afferent fibers that provide the central nervous system sensory information related to the …

Sustained reduction in blood pressure from electrical activation of the baroreflex is mediated via the central pathway of unmyelinated baroreceptors

AimsThis study aims to identify the contribution of myelinated (A-fiber) and unmyelinated (C-fiber) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity and arterial pressure. Main methodsTwo binary white noise stimulation protocols were used to electrically stimulate the aortic depressor nerve and activate reflex responses from either A-fiber (3V, 20–100Hz) or C-fiber (20V, 0–10Hz) baroreceptor in anesthetized Sprague-Dawley rats (n=10). Transfer function analysis was performed between stimulation and sympathetic nerve activity (central arc), sympathetic nerve activity and arterial pressure (peripheral arc), and stimulation and arterial pressure (Stim-AP arc). Key findingsThe central arc transfer function from nerve stimulation to splanchnic sympathetic nerve activity displayed derivative characteristics for both stimulation protocols. However, the modeled steady-state gain (0.28±0.04 vs. 4.01±0.2%·Hz−1, P<0.001) and coherence at 0.01Hz (0.44±0.05 vs. 0.81±0.03, P<0.05) were significantly lower for A-fiber stimulation compared with C-fiber stimulation. The slope of the dynamic gain was higher for A-fiber stimulation (14.82±1.02 vs. 7.21±0.79dB·decade−1, P<0.001). The steady-state gain of the Stim-AP arc was also significantly lower for A-fiber stimulation compared with C-fiber stimulation (0.23±0.05 vs. 3.05±0.31mmHg·Hz−1, P<0.001). SignificanceThese data indicate that the A-fiber central pathway contributes to high frequency arterial pressure regulation and the C-fiber central pathway provides more sustained changes in sympathetic nerve activity and arterial pressure. A sustained reduction in arterial pressure from electrical stimulation of arterial baroreceptor afferents is likely mediated through the C-fiber central pathway.

42 ELECTRICAL STIMULATION OF THE VENTRAL LATERAL PERIAQUEDUCTAL GRET (VIPAG) PRODUCES SUSTAINED REDUCTIONS IN BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE (SH) BUT NOT NORMOTENSIVE RATS

Background and Objectives: Deep brain stimulation of the vlPAG is used for the clinical treatment of chronic neuropathic pain in man. It has also been shown to produce sustained reductions in arterial pressure (AP) in hypertensive patients1. We have developed an implantable electrical stimulation system and applied it to the vlPAG of conscious, freely moving rats. Methods and Results: AP and heart rate (HR) responses to stimulation were measured via telemetry. When resting quietly, rats were stimulated for 60 min at a series of frequency steps (15, 20, 30, 40 Hz) with >30 min recovery between steps. SH rats (mean baseline AP 139 ± 10 mmHg; n = 5) showed frequency-dependent AP reductions (12 ± 4 vs 28 ± 6 mmHg; 15 vs 40 Hz; p<0.05), which persisted throughout the stimulation period. In contrast, in Wistar rats (mean baseline AP 101 ± 9mmHg; n = 4) a smaller depressor response was evoked (1 ± 2 mmHg vs 4 ± 2 mmHg; 15 vs 40 Hz), which tended to return to baseline after 20-30mins. In SH rats the depressor response was maintained throughout 3 days of continuous 10 Hz vlPAG stimulation (135 mmHg to 121 mmHg; baseline vs day 3) and associated with a reduction in the low frequency power of systolic blood pressure (1.75 to 1.51 mmHg2), suggesting sympathoinhibition. Conclusions: In conclusion, our results show that the vlPAG of the SH rat is a more effective depressor site than it is in Wistar rats. Our current studies are now determining the underlying mechanisms for this response. Reference N.K. Patel, S. Javed, S. Khan, M. Papouchado, A.L. Malizia, A.E. Pickering, and J.F.R. Paton. Deep brain stimulation relieves refractory hypertension. Neurology, 2011 76:405–407.

Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation

Device-based therapy for resistant hypertension by electrical activation of the carotid baroreflex is currently undergoing active clinical investigation, and initial findings from clinical trials have been published. The purpose of this mini-review is to summarize the experimental studies that have provided a conceptual understanding of the mechanisms that account for the long-term lowering of arterial pressure with baroreflex activation. The well established mechanisms mediating the role of the baroreflex in short-term regulation of arterial pressure by rapid changes in peripheral resistance and cardiac function are often extended to long-term pressure control, and the more sluggish actions of the baroreflex on renal excretory function are often not taken into consideration. However, because clinical, experimental, and theoretical evidence indicates that the kidneys play a dominant role in long-term control of arterial pressure, this review focuses on the mechanisms that link baroreflex-mediated reductions in central sympathetic outflow with increases in renal excretory function that lead to sustained reductions in arterial pressure.

Acute long term stimulation of the ventral periaqueductal grey (vPAG) evokes persistent hypotensive responses in spontaneously hypertensive (SH) rats

Deep brain stimulation of the ventral PAG has been used for the clinical treatment of chronic neuropathic pain. However, it also causes sustained reductions in arterial pressure (AP) in hypertensive patients. To better understand the latter, we have developed an animal model in the anaesthetised SH rat and applied long term electrical stimulation of the vPAG (30–60 min, 30Hz, 2V, 200–400μs pulse width) while measuring AP and heart rate (HR) responses. vPAG stimulation reduced AP by 14±1mmHg (basal: 139±10mmHg) in SH rats, which persisted throughout the stimulation period, whereas smaller depressor responses were evoked in Wistar rats (5±2mmHg; basal 101±9mmHg) that were poorly maintained. In the SH rat, HR decreased by 33±12bpm and was stimulus locked; a poorly maintained bradycardia of 15±3bpm was seen in Wistar rats. Our observations indicate that the vPAG of the SH rat is a more effective depressor site compared to Wistar rats, lending itself as a potential therapeutic target. Future studies will determine the mechanisms for the enhanced hypotensive effect of the vPAG in the SH versus Wistar rat.

Lowering of blood pressure during chronic suppression of central sympathetic outflow: Insight from computer simulations

1. Chronic electrical stimulation of the carotid sinuses has provided unique insight into the mechanisms that cause sustained reductions in blood pressure during chronic suppression of central sympathetic outflow. 2. Because renal denervation does not abolish the sustained fall in arterial pressure in response to baroreflex activation, this observation has seemingly challenged the concept that the kidneys play a critical role in the long-term control of arterial pressure during chronic changes in sympathetic activity. The aim of the present study was to use computer simulations to provide a more comprehensive understanding of physiological mechanisms that mediate sustained reductions in arterial pressure during prolonged baroreflex-mediated suppression of central sympathetic outflow. 3. Physiological responses to baroreflex activation under different conditions were simulated by an established mathematical model of human physiology (QHP2008; see Supporting Information (Appendix S1) provided in the online version of this article and/or http://groups.google.com/group/modelingworkshop). The model closely reproduced empirical data, providing important validation of its accuracy. 4. The simulations indicated that baroreflex-mediated suppression of renal sympathetic nerve activity does chronically increase renal excretory function but that, in addition, hormonal and haemodynamic mechanisms also contribute to this natriuretic response. The contribution of these redundant natriuretic mechanisms to the chronic lowering of blood pressure is of increased importance when suppression of renal adrenergic activity is prevented, such as after renal denervation. Activation of these redundant natriuretic mechanisms occurs at the expense of excessive fluid retention. 5. More broadly, the present study illustrates the value of numerical simulations in elucidating physiological mechanisms that are not obvious intuitively and, in some cases, not readily testable in experimental studies.

Cardiovascular reflex responses to temporal reduction in arterial pressure during dexmedetomidine infusion: a double-blind, randomized, and placebo-controlled study

The low and moderate doses of dexmedetomidine reduce arterial pressure and heart rate (HR), suggesting attenuation of sympathetic activity and dominance of cardiac-vagal activity. These autonomic responses under dexmedetomidine sedation may attenuate cardiovascular reflex responses to temporal reduction in arterial pressure, inducing a severe hypotension. We therefore investigated the effects of dexmedetomidine on cardiovascular reflex responses to temporal reduction in arterial pressure induced by the thigh cuff method. Twelve healthy men received placebo, low-dose (loading 3 microg kg(-1) h(-1) for 10 min; maintenance 0.2 microg kg(-1) h(-1) for 60 min), and moderate-dose (loading 6 microg kg(-1) h(-1) for 10 min; maintenance 0.4 microg kg(-1) h(-1) for 60 min) dexmedetomidine infusions in a randomized, double-blind, crossover study. After 70 min of drug infusion, systolic arterial pressure (SAP) and HR responses after thigh cuff deflation were evaluated as indices of cardiovascular reflex. Reduction in SAP (Delta SAP) [placebo 8 (4), low 12 (4), moderate 19 (5) mm Hg] after thigh cuff deflation was significantly greater in dexmedetomidine than placebo infusions, in a dose-dependent manner. The change in HR (Delta HR), Delta HR/Delta SAP, and the percentage restoration of SAP were lower with dexmedetomidine compared with placebo. The present results indicated that dexmedetomidine weakens arterial pressure preservation and HR responses after thigh cuff deflation, suggesting attenuated cardiovascular reflexes. Therefore, it must be cautioned that dexmedetomidine can lead to further and sustained reduction in arterial pressure during transient hypotension induced by postural changes, haemorrhage, and/or other stresses.

Influence of high salt intake on the chronic blood pressure lowering effects of the baroreflex

Prolonged electrical activation of the carotid baroreflex produces a sustained reduction in arterial pressure but whether this response is salt sensitive has not been established. To evaluate the influence of a high Na intake on the hemodynamic responses to prolonged baroreflex activation (PBA), 3 chronically instrumented dogs were maintained on normal (NS; 45 mEq/day) and high (HS; 460 mEq/day) Na intake. At each Na intake, mean arterial pressure (MAP), heart rate (HR), and Na excretion (UNaV) were monitored for 7 days before and during PBA. During NS (UNaV=40±4 mEq/day), MAP and HR were 91±3 mmHg and 73±2 bpm, respectively, before PBA. After 7 days of PBA, MAP and HR decreased 20±3 mmHg and 14±4 bpm. Subsequently, hemodynamics and Na balance were normalized by the end of a 1 week recovery period. After 7 days of HS (UNaV=446±9 mEq/day) and before PBA, MAP increased to 106 ±5 mmHg; HR was 76±1 bpm. On HS, reductions in MAP and HR were 18±6 mmHg and 12±6 bpm after 7 days of PBA, responses comparable to those seen during NS. These quantitative findings indicate that the chronic effects of PBA to lower MAP and HR are relatively unaffected by increases in Na intake above normal levels. (HL-51971).

Prolonged activation of the baroreflex: A viable approach for the treatment of hypertension?

In most patients with hypertension, arterial pressure is above the target level for control, even in those individuals taking multiple antihypertensive drugs. In this article, we review the history and current status of a nonpharmacologic approach for the treatment of hypertension--chronic electrical activation of the afferent limb of the carotid baroreflex. Recent studies in normotensive and hypertensive dogs have clearly demonstrated impressive and sustained reductions in arterial pressure and sympathetic activity during prolonged baroreflex activation. Clinical trials are now underway in Europe, and clinical investigation in the United States will begin this year to evaluate the efficacy of this therapy in patients with resistant hypertension.

Treating Hypertension

What do we really know about sympathetic outflow and blood pressure in humans? For example, in healthy normotensive young subjects, baseline sympathetic outflow can vary 2-fold to 3-fold.1,2 We also know that in healthy aging subjects, baseline sympathetic outflow can be increased dramatically with only a modest impact on vascular resistance and little or no impact on blood pressure.1 Additionally, there is no clear evidence for dramatic increases in baseline sympathetic outflow in “garden variety” essential hypertension.1 If we stop here, a position of “nihilism” about sympathetic outflow and blood pressure seems reasonable. However, when the sympathetic nervous system is destroyed by disease or surgery, blood pressure is highly labile.3 We also know that many “stressors” that evoke a pressor response also evoke marked sympathetic activation, and that the magnitude of these pressor responses can be a harbinger of future hypertension.4,5 Finally, in disease states like congestive heart failure, excessive sympathetic activation is a “bad thing.”6,7 If we emphasize these points, sympathetic vasoconstriction seems more important to blood pressure and perhaps survival. …

Role of bradykinin receptors in the renal effects of inhibition of angiotensin converting enzyme and endopeptidases 24.11 and 24.15 in conscious rabbits.

1. We tested the effects on systemic haemodynamics and renal function, of inhibition of endopeptidase (EP) 24.15 (E.C. 3.4.24.15), in conscious uninephrectomized rabbits in which the activities of angiotensin converting enzyme (ACE, E.C. 3.4.15.1) and neutral endopeptidase (EP 24.11, E.C. 3.4.24.11) were already inhibited. To test the role of bradykinin B2-receptors in mediating the effects following inhibition of these enzymes, the antagonist Hoe 140 was used. 2. Hoe 140 (0.1 mg kg-1, i.v.) did not affect resting mean arterial pressure or heart rate, but antagonized the depressor effect of right atrial administration of bradykinin. The dose-response curve for bradykinin was shifted more than 1000 fold to the right for more than 4 h. Hoe 140 approximately doubled resting urine flow and increased fractional Na+ excretion from 4.2 to 6.0%; consistent with the hypothesis that it exerts a partial agonist effect on the kidney. 3. Combined inhibition of ACE (captopril; 0.25 mg kg-1 plus 0.2 mg kg-1h-1) and EP 24.11 (SCH 39370; 3 mg kg-1 plus 3 mg kg-1h-1) was followed by a sustained reduction in arterial pressure (-6 +/- 2 mmHg) and increase in heart rate (35 +/- 7 beats min-1). There was a small increase in renal blood flow (by 6.5 +/- 3.2% relative to vehicle-treatment) without a change in glomerular filtration rate, and about a 150% increase in Na+ excretion. Hoe 140 (0.1 mg kg-1, i.v.) pretreatment did not influence the renal effects of captopril and SCH 39370, although it did appear to blunt their hypotensive and tachycardic effects. 4. When EP 24.15 was inhibited with N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Tyr-p-aminobenzoate (cFP-AAY-pAB; 5 mg kg-1 plus 3 mg kg-1h-1, i.v.) in rabbits pretreated with captopril and SCH 39370, no changes in systemic haemodynamics or renal function were observed. 5. We concluded that in conscious uninephrectomized rabbits, EP 24.15 does not play a major role in modulating renal function, at least under conditions where ACE and EP 24.11 are already inhibited. In contrast, ACE and/or EP 24.11 do modulate renal function in this model, but their influences are mediated chiefly through metabolism of peptides other than bradykinin.

Sciatic nerve stimulation induces hypotension but not renal or lumbar sympathoinhibition in hypertensive Dahl rats.

Sustained reductions in arterial pressure and sympathetic nerve activity occur after prolonged sciatic nerve stimulation in spontaneously hypertensive and pre-hypertensive Dahl salt-sensitive rats whereas these responses are not observed in renal hypertensive or Dahl resistant rats. These observations suggest that the development of post-stimulation hypotension and sympathoinhibition may be related to the genetic predisposition for hypertension rather than to the increased level of arterial pressure. However, it is not known whether the magnitude of the post-stimulation blood pressure and sympathetic nerve responses are influenced by the increased level of arterial pressure in addition to the genetic predisposition to hypertension. In the present study, we sought to determine if sustained sciatic nerve stimulation induces post-stimulation hypotension in hypertensive Dahl sensitive (DS) rats. For this purpose, mean arterial pressure (MAP), heart rate (HR), renal (RSNA) and lumbar (LSNA) sympathetic nerve activity were recorded during and after sciatic nerve stimulation in hypertensive DS rats (n = 17) fed an 8.0% NaCl diet for 7-8 weeks. Sciatic nerve stimulation increased HR (control, 443 +/- 10 b.p.m.; stimulation, 487 +/- 8 b.p.m.; p < 0.05) and tended to increase MAP, RSNA and LSNA. Two hours after stimulation, MAP was reduced (control 145 +/- 5 mmHg; recovery, 124 +/- 8 mmHg; p < 0.01) from control values. In contrast, RSNA and HR remained unchanged whereas LSNA was increased (69 +/- 20%; p < 0.05) from control values 120 min after stimulation. MAP, HR and RSNA were unchanged from control values during and for 2 h after sham stimulation in eight DS rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of arterial pressure and renal function during chronic renin inhibition

The aim of this study was to determine whether the renin inhibitor CP-71362 (Pfizer Central Research, Groton, Connecticut, USA) is capable of inducing sustained reductions in arterial pressure in sodium-depleted dogs and to examine the changes in renal function associated with chronic renin inhibition. In addition, we also examined the chronic effects on renal function and blood pressure of the angiotensin converting enzyme (ACE) inhibitor enalaprilat. Infusion of CP-71362 (1.1 micrograms/kg per min, intravenously) for 7 days decreased mean arterial pressure from 87 +/- 3 to 75 +/- 2 mmHg, while causing no significant changes in sodium excretion, the glomerular filtration rate, or effective renal plasma flow. Plasma renin activity was suppressed to undetectable levels throughout the 7 days of CP-71362 infusion. Infusion of enalaprilat (4 mg/kg per day) for 7 days in sodium-depleted dogs decreased mean arterial pressure (from 85 +/- 2 to 64 +/- 3 mmHg) and renal vascular resistance, and increased effective renal plasma flow and sodium excretion, but caused no significant changes in the glomerular filtration rate. Thus CP-71362 is a potent inhibitor of dog plasma renin, and we observed no waning of this inhibitory effect of CP-71362's hypotensive actions over 7 days. The mechanisms responsible for the differences in the blood pressure and renal responses to CP-71362 and ACE inhibition are not clear, but may be dose-related or due to differences in the distribution of these compounds to various tissues, including the kidney.

Angiotensin inhibition in severe heart failure: Acute central and limb hemodynamic effects of captopril with observations on sustained oral therapy

The systemic, pulmonary, and limb circulatory responses to the angiotensin-converting enzyme inhibitor, captopril, were determined in 10 patients with severe, chronic heart failure. Immediate effects include sustained reductions in arterial pressure and pulmonary capillary wedge pressure and improvement in cardiac output, as reported with other vasodliator drugs. Calf vascular resistance did not change despite substantial lowering of total systemic vascular resistance, indicating that arteriolar dilatation occurred on a selective basis. Transient reduction in mean right atrial pressure paralleled slight calf venodillatation, but effects upon the resistance vasculature predominated. Plasma renin activity and norepinephrine concentrations increased after therapy in the acute phase as plasma aldosterone levels consistently fell. During maintenance oral treatment over 7 to 15 months (median, 11.5 months), patients displayed symptomatic benefit, improved functional capacity, and greater exercise tolerance. No major adverse reactions developed. These findings suggest that angiotensin converting enzyme inhibition with captopril in congestive heart failure patients improves cardiocirculatory function through selective arteriolar dilatation. The reordering of regional blood flow which appears to result from release of angiotensin-mediated vasoconstriction, as well as the suppression of aldosterone, may underlle the prolonged benefit observed in these patients. This oral vasodilator appears to represent an effective adjunct for the treatment of advanced, chronic heart failure refractory to conventional measures.

FAILURE OF SARALASIN TO PREDICT A RESPONSE TO SURGERY IN RENOVASCULAR HYPERTENSION

Arteriography in two patients with renovascular hypertension suggested fibromuscular hyperplasia, mainly affecting the right renal artery. When saralasin was infused intravenously there was no fall in blood-pressure in either patient. However, both had a raised renal-vein plasma-renin activity on the affected side, relative to the unaffected kidney. Auto-transplantation resulted in a sustained reduction in arterial pressure in both patients. A negative saralasin test should not necessarily exclude further investigation of young patients with severe hypertension.