PERSISTENT REDUCTION IN RENAL NERVE GROWTH-FACTOR MESSENGER-RNA AFTERPERINDOPRIL TREATMENT OF YOUNG SPONTANEOUSLY HYPERTENSIVE RATS

Nerve growth factor (NGF) determines sympathetic innervation of target tissues, and NGF levels are increased in young spontaneously hyperten sive rats (SHR). Angiotensin call affect NGF levels, and the persisten t reduction in blood pressure after brief angiotensin-converting enzym e inhibition in young-SHR may involve long-term changes in NGF and sym pathetic innervation. We measured the relative abundance of renal NGF mRNA by reverse transcription-polymerase chain reaction in SHR during and after treatment from B to 10 weeks of age with vehicle, perindopri l (3 mg/kg per day), the bradykinin beta(2) antagonist Hoe 140 (0.5 mg /kg per day), both perindopril and Hoe 140, or angiotensin II (Ang II; 200 ng/kg per minute). Glomerular filtration rates were estimated at 10 and 20 weeks of age. At 10 weeks of age, Ang II caused a significan t (P < .01) increase and perindopril caused a significant (P < .01) de crease in renal NGF mRNA levels. Blockade of the bradykinin B-2, recep tor during perindopril treatment attenuated (P < .05) the reduction in NGF mRNA levels. Renal NGF mRNA (P = .005) and blood pressure (P < .0 01) remained significantly lower than control 10 weeks after perindopr il treatment was stopped. The partial reduction in blood pressure at 2 0 weeks of age in rats that had received perindopril and Hoe 140 was n ot associated with any difference in renal NGF mRNA. Perindopril-induc ed long-term reduction in renal NGF mRNA levels may decrease sympathet ic innervation and thereby contribute to thr long-term posttreatment b lood pressure reduction.