title: Role of cardiac hypertrophy in reducing the sensitivity of cardiopulmonary reflex control of renal sympathetic nerve activity in spontaneously hypertensive rats.
abstract: The gain of the volume-sensitive cardiopulmonary reflex (VSCR) is impaired in spontaneously hypertensive rats (SHR). Sensitivity of VSCR control of efferent renal sympathetic nerve activity (RSNA) in SHR is restored when cardiac hypertrophy and hypertension are reduced by enalapril treatment. The present study investigated which of these two parameters, cardiac hypertrophy or hypertension, has more influence on the impairment of VSCR control of RSNA in SHR. Rats (SHR or Wistar-Kyoto (WKY) rats) were treated with enalapril (10 mg/kg per day; SHRE and WKYE groups, respectively) or hydralazine (5 mg/kg per day; SHRH and WKYH groups, respectively) mixed in their food for 1 month. Control SHR and WKY rats were fed a normal diet. After the treatment regimen, the VSCR was evaluated by determining the decrease in RSNA elicited by acute isotonic saline volume expansion. Mean arterial pressure (MAP) was assessed via an intrafemural catheter and cardiac hypertrophy was determined by the left ventricular (LV) weight/bodyweight (BW) ratio. Afferent baroceptor nerve activity (BNA) was also evaluated during volume expansion to verify participation of the baroreflex. Volume expansion produced an attenuated renal sympathoinhibitory response in SHR compared with WKY rats. Enalapril treatment restored the volume expansion-induced decrease in RSNA in SHRE (-41 +/- 8%) compared with WKY rats (-44 +/- 3%). Although both enalapril and hydralazine treatment reduced MAP in SHR (P < 0.01; 126 +/- 5, 133 +/- 6 and 160 +/- 6 mmHg in SHRE, SHRH and SHR, respectively), hydralazine did not restore the sensitivity of VSCR control of RSNA in SHRH. Spontaneously hypertensive rats with established hypertension had a higher LV/BW ratio compared with WKY rats (3.22 +/- 0.14 vs 1.98 +/- 0.06 mg/g, respectively; P < 0.01). Enalapril reduced the LV/BW ratio in SHRE (2.30 +/- 0.07 mg/g; P < 0.01). Although hydralazine reduced LV hypertrophy, there was a weaker reduction in SHRH (2.68 +/- 0.04 mg/g; P < 0.05) compared with SHRE. There was no statistically significant difference among the WKY rat, WKYE and WKYH groups (P > 0.05). There was no change in afferent BNA during volume expansion in normal or hypertensive animals. Taken together, these results indicate that the impairment of VSCR control of RSNA in the SHR model of hypertension correlates better with the magnitude of cardiac hypertrophy than the level of arterial pressure.
authors.affiliation: Department of Physiological Sciences, Centre of Health Sciences, Federal University of Espírito Santo, Vitória, Brazil.
authors.forename: Tadeu Uggere
authors.initials: TU
authors.lastname: de Andrade
authors.forename: Gláucia R
authors.initials: GR
authors.lastname: Abreu
authors.forename: Margareth R
authors.initials: MR
authors.lastname: Moysés
authors.forename: Antônio
authors.initials: A
authors.lastname: de Melo Cabral
authors.forename: Nazaré S
authors.initials: NS
authors.lastname: Bissoli
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017704:Baroreflex / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D006332:Cardiomegaly / Q000503:physiopathology*; D004656:Enalapril / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000294:innervation*; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D011311:Pressoreceptors / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D000959:Antihypertensive Agents; D006830:Hydralazine; D004656:Enalapril