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

Abstract

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...

Interactions between the sympathetic nervous system and the kidneys in arterial hypertension

“…Similar to experimental data [76] acute arterial pressure reduction by 15 mm Hg with dihydralazine but not with the ACE inhibitor, enalaprilat, elicited increased sympathetic activity in patients with renovascular hypertension as evidenced by a 50% rise in total body norepinephrine spillover and a 15% increase in peroneal sympathetic nerve activity [77]. In contrast, enalaprilat but not dihydralazine increased renal norepinephrine spillover by 40% in renovascular hypertensive patients [77].…”

Altered Hepatic Gene Expression Profiles Associated With Myocardial Ischemia

“…Because the liver has rich sympathetic and parasympathetic innervation, [17][18][19] it is possible that sympathetic hyperactivity affects hepatic gene expression. Although hydralazine has been reported to activate sympathetic nerves, 20,21 we observed no differences in gene expression in the hydralazine-treated group compared with the shamoperated group (data not shown). Therefore, autonomic nerves seemed to have little effect on hepatic gene expression determined in this study.…”

Circulating angiotensin II and dietary salt: Converging signals for neurogenic hypertension

“…Studies in patients with chronic angiotensin-dependent renovascular hypertension generally have demonstrated sympathetic activation whose magnitude is correlated with circulating Ang II concentrations [5]. Furthermore, angiotensin-converting enzyme inhibitors [6] and angiotensin receptor blockers [7] laboratory studies, we direct most attention to work in experimental animals. The literature supports the concept that Ang II mediates sympathoexcitation in many animal models of hypertension [4].…”