Donna H Wang1, Yajuan Zhao. 1. Department of Medicine, Michigan State University, East Lansing, 48824, USA. donna.wang@ht.msu.edu
Abstract
OBJECTIVE: A unique model of hypertension developed in our laboratory shows that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to salt load with a significant rise in blood pressure. Considering that capsaicin impairs the micturition reflex, increased retention of urine in the bladder of capsaicin-treated rats may lead to nephropathy and therefore to an increase in blood pressure. The present study was designed to test the hypothesis that abnormalities in renal function and blood pressure in this model are independent of urine retention, and are reversible when a high-salt diet is withdrawn. DESIGN AND METHODS: Newborn Wistar rats were given either 50 mg/kg capsaicin subcutaneously or vehicle on the first and second days of life. After weaning, one set of male rats was treated for 3 weeks with: capsaicin pretreatment plus high-sodium diet (4%, CAP-HS), capsaicin plus normal-sodium diet (0.5%, CAP-NS), control plus high-sodium diet (CON-HS), and control plus normal sodium diet (CON-NS). The other set of male rats was given the same treatment for 4 weeks except that the two high-salt-treated groups were switched to normal salt (CAP-HS-NS and CON-HS-NS) for the last week. Chronic bladder catheterization was carried out in all rats to maintain free flow of urine. Western blot was used for measurement of the capsaicin (vanilloid) receptor levels in dorsal root ganglia. Radioimmunoassay was used for measurement of plasma renin activity and plasma aldosterone levels. RESULTS: Capsaicin (vanilloid) receptor contents in dorsal root ganglia were markedly decreased in all capsaicin-treated groups. Plasma renin activity and plasma aldosterone levels were higher in CAP-HS rats than in CON-HS rats, but were not statistically different between CAP-HS-NS and CON-HS-NS rats. Urine Na excretion but not urine volume was decreased and water intake increased in CAP-HS compared with CON-HS, but these parameters were not statistically different between CAP-HS-NS and CON-HS-NS rats. Although systolic blood pressure and mean arterial pressure were higher in CAP-HS and CAP-HS-NS rats than in CON-HS and CON-HS-NS rats, they were higher in CAP-HS than in CAP-HS-NS rats. CONCLUSION: Despite elimination of urine retention, sensory denervation impairs renal function and leads to an increase in blood pressure in response to high salt intake. The abnormalities in renal function and blood pressure in sensory denervated rats are reversible, at least in part, when high salt intake is withdrawn. These data support the hypothesis that sensory innervation counterbalances the pro-hypertensive systems and serves as a modulator to control salt sensitivity and cardiovascular function.
OBJECTIVE: A unique model of hypertension developed in our laboratory shows that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to salt load with a significant rise in blood pressure. Considering that capsaicin impairs the micturition reflex, increased retention of urine in the bladder of capsaicin-treated rats may lead to nephropathy and therefore to an increase in blood pressure. The present study was designed to test the hypothesis that abnormalities in renal function and blood pressure in this model are independent of urine retention, and are reversible when a high-salt diet is withdrawn. DESIGN AND METHODS: Newborn Wistar rats were given either 50 mg/kg capsaicin subcutaneously or vehicle on the first and second days of life. After weaning, one set of male rats was treated for 3 weeks with: capsaicin pretreatment plus high-sodium diet (4%, CAP-HS), capsaicin plus normal-sodium diet (0.5%, CAP-NS), control plus high-sodium diet (CON-HS), and control plus normal sodium diet (CON-NS). The other set of male rats was given the same treatment for 4 weeks except that the two high-salt-treated groups were switched to normal salt (CAP-HS-NS and CON-HS-NS) for the last week. Chronic bladder catheterization was carried out in all rats to maintain free flow of urine. Western blot was used for measurement of the capsaicin (vanilloid) receptor levels in dorsal root ganglia. Radioimmunoassay was used for measurement of plasma renin activity and plasma aldosterone levels. RESULTS:Capsaicin (vanilloid) receptor contents in dorsal root ganglia were markedly decreased in all capsaicin-treated groups. Plasma renin activity and plasma aldosterone levels were higher in CAP-HS rats than in CON-HS rats, but were not statistically different between CAP-HS-NS and CON-HS-NSrats. Urine Na excretion but not urine volume was decreased and water intake increased in CAP-HS compared with CON-HS, but these parameters were not statistically different between CAP-HS-NS and CON-HS-NSrats. Although systolic blood pressure and mean arterial pressure were higher in CAP-HS and CAP-HS-NS rats than in CON-HS and CON-HS-NS rats, they were higher in CAP-HS than in CAP-HS-NS rats. CONCLUSION: Despite elimination of urine retention, sensory denervation impairs renal function and leads to an increase in blood pressure in response to high salt intake. The abnormalities in renal function and blood pressure in sensory denervated rats are reversible, at least in part, when high salt intake is withdrawn. These data support the hypothesis that sensory innervation counterbalances the pro-hypertensive systems and serves as a modulator to control salt sensitivity and cardiovascular function.