Increased Sympathetic Nerve Activity in Renovascular Hypertension

Johansson, Mats; Elam, Mikael; Rundqvist, Bengt; Eisenhofer, Graeme; Herlitz, Hans; Lambert, Gavin W.; Friberg, Peter

doi:10.1161/01.cir.99.19.2537

Cited by 159 publications

(116 citation statements)

References 31 publications

(23 reference statements)

Supporting

Mentioning

109

Contrasting

Unclassified

Order By: Relevance

“…9 -11 Importantly, examining the same patient with or without renal hypertension did not show any difference in total noradrenaline spillover. 9,11 Reports of noradrenaline turnover in 2K1C rabbits have found no change in turnover from a range of tissues suggesting that there is not a generalized change in sympathetic activity in this model. 12 Thus there is a paradox.…”

mentioning

confidence: 68%

Sympathetic Responses to Stress and Rilmenidine in 2K1C Rabbits

Head

Burke

2004

Hypertension

View full text Add to dashboard Cite

Abstract-We determined whether the sympathetic excitatory responses to environmental stressors and the sympathoinhibitory responses to rilmenidine are altered by renovascular hypertension. Rabbits were made hypertensive with a clip on the right renal artery, and a left renal nerve recording electrode was implanted. After 3 or 6 weeks, the animals were given air-jet stress and loud noise stress before and after intravenous rilmenidine. Three and 6 weeks after renal clipping, mean arterial pressure was 28% and 36% greater than preclip values. Air-jet stress elicited a marked increase in renal sympathetic nerve activity, mean arterial pressure, and heart rate. Renal sympathetic nerve activity responses were much greater in hypertensive rabbits, but the pressor responses were similar to those observed in normotensive animals. Acute administration of rilmenidine decreased blood pressure more in hypertensive animals but with a much lesser inhibition of sympathetic activity. Rilmenidine markedly reduced increased sympathetic activity during air-jet stress in 3-week clipped rabbits but to a lesser extent in the other groups. These studies show that while sympathetic responses to stress were markedly enhanced in renal clip hypertensive rabbits, they did not result in greater pressor responses, thus suggesting that vascular neuroeffector mechanisms were not altered. By contrast, the increased effects of rilmenidine suggest a much greater contribution to the hypertension by the sympathetic nervous system, but one that is caused by an enhanced "nonvascular" neuroeffector mechanism. As such, sympathoinhibitory agents such as rilmenidine are very suitable and very effective agents for the treatment of renovascular hypertension. Key Words: renal nerves Ⅲ hypertension Ⅲ stress Ⅲ sympathetic nervous system Ⅲ rabbits Ⅲ blood pressure Ⅲ heart rate T here has been a long-standing interest in the role of the sympathetic nervous system in hypertension, but more so in view of increasing evidence that it can contribute to the long-term setting of blood pressure. 1 In renovascular hypertension, there is much evidence for a greater dependence of the hypertension on the sympathetic nervous system. 2 A greater depressor response to ganglion blockade has been observed in renal wrap hypertensive rats. 3 Studies in the rabbit by Cox and Bishop showed that during angiotensin (Ang) infusion, the hypertension was initially caused by Ang-mediated vasoconstriction that subsided and was replaced by a greater neurogenic component. 4 One of the major difficulties in determining the contribution of the sympathetic nervous system in hypertension has been in making direct comparisons of microvolt values between different groups. Recently, we developed a novel method for comparing sympathetic activity between groups of animals 5 and found that renal sympathetic nerve activity (RSNA) is not increased but initially decreased or unchanged in 2-kidney 1-clip (2K1C) hypertensive rabbits. 6 Studies in renal wrap 7 and chronic Ang-induced hypertension 8 support...

show abstract

mentioning

confidence: 68%

Sympathetic Responses to Stress and Rilmenidine in 2K1C Rabbits

Head

Burke

2004

Hypertension

View full text Add to dashboard Cite

show abstract

“…The present study population represents a subset of patients referred to in previous publications. 2,10 All patients had hypertension and renal artery stenosis Ն50% according to angiography. Overall, 57 patients were examined.…”

Section: Subjectsmentioning

confidence: 99%

“…1,2 Previous data, obtained in experimental models, indicate a positive interaction between the renin-angiotensin and the sympathetic nervous systems. 3 Therefore, in renovascular hypertension it may be favorable to use a therapeutic modality that does not reflexly further increase heart rate, renin secretion, and sympathetic nervous activity.…”

mentioning

confidence: 99%

Differentiated Response of the Sympathetic Nervous System to Angiotensin-Converting Enzyme Inhibition in Hypertension

et al. 2000

Self Cite

View full text Add to dashboard Cite

Abstract-Hypertension with renal artery stenosis is associated with both an activated renin-angiotensin system and elevated sympathetic activity. Therefore, in this condition it may be favorable to use a therapeutic modality that does not reflexly increase heart rate, renin secretion, and sympathetic nervous activity. The purpose of the present study was to assess overall, renal, and muscle sympathetic activity after short-term administration of an angiotensin-converting enzyme inhibitor (enalaprilat) and a nonspecific vasodilator (dihydralazine) to hypertensive patients with renal artery stenosis. Forty-eight patients undergoing a clinical investigation for renovascular hypertension were included in the study. An isotope dilution technique for assessing norepinephrine spillover was used to estimate overall and bilateral renal sympathetic nerve activity. In 11 patients simultaneous intraneural recordings of efferent muscle sympathetic nerve activity were performed. Thirty minutes after dihydralazine administration, mean arterial pressure fell by 15%, whereas plasma angiotensin II, muscle sympathetic nerve activity, heart rate, and total body norepinephrine spillover increased (PϽ0.05 for all). In contrast, after enalaprilat administration a fall in arterial pressure similar to that for dihydralazine was followed by decreased angiotensin II levels and unchanged muscle sympathetic nerve activity, heart rate, and total body norepinephrine spillover, whereas renal norepinephrine spillover increased by 44% (PϽ0.05). Acute blood pressure reduction by an angiotensin-converting enzyme inhibitor provokes a differentiated sympathetic response in patients with hypertension and renal artery stenosis, inasmuch that overall and muscle sympathetic reflex activation are blunted, whereas the reflex renal sympathetic response to blood pressure reduction is preserved. (Hypertension. 2000;36:543-548.)Key Words: hypertension, renovascular Ⅲ sympathetic nervous system Ⅲ renin-angiotensin system R enovascular hypertension is a condition associated with both an activated renin-angiotensin system and elevated sympathetic nerve activity. 1,2 Previous data, obtained in experimental models, indicate a positive interaction between the renin-angiotensin and the sympathetic nervous systems. 3 Therefore, in renovascular hypertension it may be favorable to use a therapeutic modality that does not reflexly further increase heart rate, renin secretion, and sympathetic nervous activity. It is well known that certain drugs used in cardiovascular medicine affect various indices of sympathetic activity. For example, sympathetic activity increases in response to nonspecific vasodilators, whereas therapy with angiotensin-converting enzyme (ACE) inhibitors has demonstrated reduced peroneal sympathetic activity. 4 Thus, it appears that vasodilators and ACE inhibitors produce different sympathetic nerve responses; the effects of the latter could be due to either a direct-acting central mechanism 5,6 or a reduction of angiotensin II (Ang II) facilitatory e...

show abstract

“…hereas the notion that hypertension in human patients 1,2 and animal models [3][4][5] is attributable to an augmented central sympathetic outflow to the heart or peripheral vasculature is well accepted, the mechanism that underlies sympathetic overactivity during hypertension requires further delineation. Recent studies 6 -8 implicate an abnormality of the nitric oxide (NO) system in the brain in hypertension.…”

mentioning

confidence: 99%

Downregulation of Basal iNOS at the Rostral Ventrolateral Medulla Is Innate in SHR

2003

View full text Add to dashboard Cite

Abstract-We demonstrated recently that a significant reduction in both the molecular synthesis and functional expression of inducible nitric oxide synthase (iNOS) in the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor outflow, underlies the augmented sympathetic vasomotor tone during hypertension. This study further evaluated the hypothesis that this downregulation of basal iNOS at the RVLM during hypertension is innate. In adult spontaneously hypertensive rats (SHR) treated for 4 weeks with the antihypertensive captopril to normalize elevated blood pressure or in young prehypertensive SHR, the significantly lower iNOS mRNA and protein levels at the ventrolateral medulla under basal conditions or on activation by microinjection bilaterally into the RVLM of lipopolysaccharide (10 ng) remained unaltered. The retarded efficacy of lipopolysaccharide (10 ng) to elicit cardiovascular depression (hypotension, bradycardia, and reduction in sympathetic vasomotor tone) also persevered in captopril-treated adult or young normotensive SHR. On the other hand, compared with Wistar-Kyoto normotensive rats, the magnitude of cardiovascular depression induced in adult SHR by local administration into the RVLM of the NO precursor L-arginine (40 nmol) was significantly smaller. In addition, microinjection bilaterally into the RVLM of a selective iNOS inhibitor, aminoguanidine (125 or 250 pmol), was discernibly less efficacious in unmasking hypertension, tachycardia, and the increase in sympathetic vasomotor tone in adult SHR. We conclude that a predisposed reduction in molecular synthesis and functional expression of basal iNOS in the RVLM is associated with the sympathetic vasomotor overactivity during hypertension. Key Words: nitric oxide synthase Ⅲ hypertension, essential Ⅲ nitric oxide Ⅲ blood pressure Ⅲ heart rate Ⅲ nervous system, autonomic W hereas the notion that hypertension in human patients 1,2 and animal models 3-5 is attributable to an augmented central sympathetic outflow to the heart or peripheral vasculature is well accepted, the mechanism that underlies sympathetic overactivity during hypertension requires further delineation. Recent studies 6 -8 implicate an abnormality of the nitric oxide (NO) system in the brain in hypertension. Originally identified as an endothelium-derived vascular relaxing factor, 9 NO is now known to play an active role in central cardiovascular regulation. 6,7 In the rostral ventrolateral medulla (RVLM), where premotor neurons that provide the tonic sympathetic vasomotor drive are located, 10 we demonstrated 11 recently that whereas small amounts of NO generated by neuronal NO synthase (nNOS) in the RVLM promote sympathoexcitation, large amounts of NO produced by inducible NOS (iNOS) elicit sympathoinhibition. Under physiological conditions, the prevalence of nNOS over iNOS activity and the associated dominance of sympathoexcitation over sympathoinhibition are responsible for the maintenance of neurogenic vasomotor tone and stable arterial pressure elici...

show abstract

Increased Sympathetic Nerve Activity in Renovascular Hypertension

Abstract: This study unequivocally demonstrates elevated sympathetic nerve activity in patients with renovascular hypertension. The adrenergic overactivity may contribute to the blood pressure elevation and perhaps also to the high cardiovascular mortality in renovascular hypertension.

Cited by 159 publications

References 31 publications

Sympathetic Responses to Stress and Rilmenidine in 2K1C Rabbits

Sympathetic Responses to Stress and Rilmenidine in 2K1C Rabbits

Differentiated Response of the Sympathetic Nervous System to Angiotensin-Converting Enzyme Inhibition in Hypertension

Downregulation of Basal iNOS at the Rostral Ventrolateral Medulla Is Innate in SHR

Contact Info

Product

Resources

About