Antihypertensive mechanisms of chronic captopril or N-acetylcysteine treatment in L-NAME hypertensive rats.

Hypertension due to chronic inhibition of NO synthase (NOS) by Nomega-nitro-L-arginine methyl ester (L-NAME) administration is characterized by both impaired NO-dependent vasodilation and enhanced sympathetic vasoconstriction. The aim of our study was to evaluate changes in the participation of major vasoactive systems in L-NAME-treated rats which were subjected to simultaneous antihypertensive (captopril) or antioxidant (N-acetylcysteine, NAC) treatment. Three-month-old Wistar males treated with L-NAME (60 mg/kg/day) for 5 weeks were compared to rats in which L-NAME treatment was combined with simultaneous chronic administration of captopril or NAC. Basal blood pressure (BP) and its acute responses to consecutive i.v. injections of captopril (10 mg/kg), pentolinium (5 mg/kg), L-NAME (30 mg/kg), tetraethylammonium (TEA, 16 mg/kg) and nitroprusside (NP, 20 microg/kg) were determined in conscious rats at the end of the study. The development of L-NAME hypertension was prevented by captopril treatment, whereas NAC treatment caused only a moderate BP reduction. Captopril treatment normalized the sympathetic BP component and significantly reduced residual BP (measured at full NP-induced vasodilation). In contrast, chronic NAC treatment did not modify the sympathetic BP component or residual BP, but significantly enhanced NO-dependent vasodilation. Neither captopril nor NAC treatment influenced the compensatory increase of TEA-sensitive vasodilation mediated by endothelium-derived hyperpolarizing factor in L-NAME-treated rats. Chronic captopril treatment prevented L-NAME hypertension by lowering of sympathetic tone, whereas chronic NAC treatment attenuated L-NAME hypertension by reduction in the vasodilator deficit due to enhanced NO-dependent vasodilation.

The role of renal sympathetic nervous system in the pathogenesis of ischemic acute renal failure.

We investigated the role of renal sympathetic nervous system in the progression of ischemia/reperfusion-induced acute renal failure in rats. Acute renal failure was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Renal venous plasma norepinephrine concentrations markedly and significantly increased immediately after reperfusion, thereafter, the increased level declined but remained higher even at 24 h after reperfusion. Renal sympathetic nerve activity was significantly augmented during the renal ischemia. Renal denervation or the administration of pentolinium, a ganglion blocking agent, (5 mg/kg i.v.) at 5 min before ischemia attenuated the ischemia/reperfusion-induced renal dysfunction and histological damage, such as proteinaceous casts in tubuli and tubular necrosis. The elevation of renal venous norepinephrine levels after reperfusion was suppressed by renal denervation or pentolinium treatment. Thus, a surgical or pharmacological blockade of renal sympathetic nerve prevents the progression of ischemia/reperfusion-induced acute renal failure, thereby suggesting that renal sympathetic nervous system plays an important role in the development of the ischemic acute renal failure.

Use of pentolinium in postoperative hypertension resistant to sodium nitroprusside.

Five patients with systemic arterial hypertension occurring in the postoperative period and resistant to sodium nitroprusside are described. The hypertension was associated with evidence of increased activity of the autonomic and renin-angiotensin systems. Sympathetic blockade using the ganglion blocking agent, pentolinium, enabled the arterial pressure to be controlled adequately in all patients. This was associated with a decrease in catecholamine concentrations, plasma renin activity and angiotensin II concentrations.

Autonomic hyperreflexia: pathophysiology and medical management.

Integral to the successful rehabilitation of patients with myelopathies is the prompt and proper management of autonomic hyperreflexia. More than 80% of tetraplegic and high paraplegic patients experience this syndrome of disordered autonomic homeostasis during their rehabilitation. Successful prevention and management require a clear understanding of the pathophysiology, aided in particular by recent clarification of catecholamine activity in spinal man. Prevention is accomplished through optimal general medical care, as well as proper bladder, bowel and skin management. Treatment of the acute episode requires prompt identification and removal of the offending stimulus, and occasionally the administration of a potent direct vasodilator (diazoxide, nitroprusside). Recurrent episodes are approached through definitive management of the primary problem provoking the stimulus, accompanied by symptomatic prevention of the syndrome (mecamylamine, phenoxybenzamine).

Technical and pharmacologic management of distal hypotension during repair of coarctation of the aorta.

Neurologic and abdominal complications can occur in the postoperative period of aortic coarctation repair, ischemia being the pathogenic factor most likely to be involved. This study was designed to evaluate the extent of the hemodynamic changes proximal and distal to the coarctation at the time of cross-clamping, as well as the effects of pentolinium and isoproterenol upon the hemodynamic changes. Included in the study were 17 patients with adult type coarctations who had dual hemodynamic monitoring. During cross-clamping, there was an increase in the gradient between proximal and distal pressures, with severe distal hypotension (< 50 mm Hg) occurring in six patients. Isoproterenol corrected the hypotension in five patients, but the sixth required a surgical shunt. Pentolinium was effective for the treatment of proximal hypertension; however, it also decreased distal pressure. The ligation of collateral vessels was associated with a decrease in distal pressures as well. During cross-clamping, pentolinium was useful for the management of proximal hypertension and isoproterenol increased the distal pressures in some of the patients who presented distal hypotension. However, because of the difficulties in predicting the individual response, their administration would be best guided by dual pressure monitoring. It is postulated that the recognition and proper treatment of distal hypotension may be an important factor in the prophylaxis of postoperative complications.

Pentolinium for control of reflex hypertension in spinal cord injured patients.

Ganglioplegia was produced by intravenous infusion of pentolinium tartrate 5 mg to control reflex hypertension in 29 patients with chronic spinal cord injuries undergoing 32 elective surgical procedures. The patient group with lesions above the first thoracic segment (T1) demonstrated significant but moderate intraoperative elevation of both systolic and diastolic pressure whether pentolinium was given prior to or during surgical stimulation. Patients with lesions below T1 had no significant pressure elevations with either mode of therapy. Pentolinium ganglioplegia can safely maintain blood pressure within reasonable limits in these patients; some increase in dosage may be required in patients with lesions above T1.

Autonomic hyperreflexia: intraoperative control with pentolinium tartrate.

Autonomic hyperreflexia (AH) is a clinical syndrome associated with the development of severe hypertension. It usually occurs in patients with high-level chronic spinal cord injury, and in response to stimuli associated with the distension of a hollow viscus. Protection against AH by the prophylactic use of pentolinium tartrate (Ansolysen) in doses of 10-15 mg was evaluated in a controlled study of unanaesthetized patients who were either quadriplegic or paraplegic and who were undergoing rectal and bladder surgical procedures. When compared with the control group, the systolic and diastolic arterial pressures during operation were significantly less (P less than 0.05) and remained near normal in the pretreated patients. The use of pentolinium to prevent or control AH during surgical procedures in patients with chronic spinal cord damage is a simple alternative to spinal or general anaesthesia.

Pentolinium in the management of autonomic hyperreflexia.

Patients with high spinal cord injuries frequently will develop a syndrome of autonomic hyperreflexia when stimulated by urological instrumentation. Severe sustained hypertension is the most hazardous component encountered during this reaction. Herein we report a series of patients exhibiting this condition who were managed safely and successfully by the use of the ganglionic blocking agent, pentolinium.

Acute controlled hypotension and EEG in patients with hypertension and cerebrovascular disease.

Forty-seven patients with hypertension and/or cerebrovascular disease were examined by an acute controlled hypotension test. This was performed by intravenous administration of the ganglionic blocking agent pentholonium and head-up tilting on a pivoted table with observation of the clinical neurological state and simultaneous EEG recording. Blood pressure was reduced by approximately 55% and brought to the point where signs of general cerebral ischaemia developed. By tilting back to horizontal the blood pressure returned to near the normal level. No change in focal neurological symptoms or changes in the EEG were observed, and it is concluded that the majority of hypertensive patients with or without previous stroke do tolerate normalization of their blood pressure. Controlled hypotension with tilting seems a simple and valuable test for excluding those few subjects who might not tolerate a blood pressure reduction. Whether EEG monitoring during the test increases the value of the test has not been answered.