title: Enalapril attenuates the exaggerated sympathetic response to physical stress in prenatally programmed hypertensive rats.
abstract: Adulthood hypertension can be prenatally programmed by maternal dietary protein deprivation. We have shown that the sympathetically mediated pressor response to physical stress is exaggerated in prenatally programmed hypertensive (PPH) rats. The mechanisms underlying this abnormal responsiveness remain undetermined. The renin-angiotensin system is known to affect sympathetic nerve activity. Therefore, the purpose of this study was to determine whether inhibition of the renin-angiotensin system attenuates the enhanced sympathetic and pressor responses to physical stress in PPH rats. Changes in renal sympathetic nerve activity and blood pressure in response to hindlimb contraction, hindlimb stretch, and hindlimb intra-arterial capsaicin administration were assessed in control and PPH rats treated (from age 3 weeks) with either vehicle or the angiotensin-converting enzyme inhibitor enalapril. Conscious resting systolic arterial pressure was significantly greater in PPH rats (142±5 mm Hg) than in control (128±2 mm Hg) after vehicle treatment (P<0.05). Resting systolic pressure was reduced by enalapril treatment in PPH rats (125±2 mm Hg) but had no effect in control (128±2 mm Hg). The pressor and renal sympathetic responses to muscle contraction and stretch were significantly higher in decerebrate PPH rats than in decerebrate control in vehicle-treated groups. Responses to capsaicin were variable. Enalapril significantly attenuated the enhanced contraction-induced elevations in mean pressure (vehicle, 45±6 mm Hg; enalapril, 21±3 mm Hg) and renal sympathetic activity (vehicle, 175±22%; enalapril, 89±23%) in PPH rats. Its effects were similar on responses to stretch in PPH rats but were equivocal during capsaicin administration. The results suggest that the renin-angiotensin system contributes to the enhancement of the renal sympathetic and pressor responses to physical stress in PPH rats.
authors.affiliation: University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9174. scott.smith@utsouthwestern.edu, michel.baum@utsouthwestern.edu.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mizuno
authors.forename: German
authors.initials: G
authors.lastname: Lozano
authors.forename: Khurrum
authors.initials: K
authors.lastname: Siddique
authors.forename: Michel
authors.initials: M
authors.lastname: Baum
authors.forename: Scott A
authors.initials: SA
authors.lastname: Smith
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D005082:Physical Exertion / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D018689:Sensory System Agents / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000959:Antihypertensive Agents; D018689:Sensory System Agents; D004656:Enalapril; D002211:Capsaicin
keywords: autonomic nervous system; blood pressure; diet, protein-restricted; embryonic and fetal development; exercise; hypertension; renin-angiotensin system