CARDIAC HYPERTROPHY FROM 1K-1C
HYPERTENSION BUT NOT EXERCISE TRAINING ABOLISHES ANP SENSITISATION OF
BAROREFLEX BRADYCARDIA. S.G. Hood and R.L. Woods*. Howard Florey Institute, University of
Melbourne, 3010, Australia. Our previous studies (Thomas et
al, Hypertension, 1997 & 1998) showed that, in normotensive rats but
not in spontaneously hypertensive rats (SHR), ANP enhanced the reflex
bradycardia induced by rapid ramp increases in blood pressure (BP). If BP and heart size were completely
normalised in SHR, reflex actions of ANP were restored. ANP's lack of action in SHR was not due to
raised BP, per se, but was linked to
cardiac hypertrophy (CH); even modest (~8%) increases in left ventricle/body
weight ratio (LV/BW) prevented ANP action.
Our present aims were to determine if this link with ANP applied also to
physiological CH, induced by chronic exercise training (EX), and to
pathological CH of one-kidney, one-clip (1K-1C) renovascular hypertension. Munich-Wistar (MW) rats (EX; n=7), allowed
free access to a running wheel in their home cages, ran 3-7 km per day for
10-12 weeks, resulting in significant (P<0.05) CH (LV/BW = 2.73 ± 0.09 mg/g) compared with
sedentary controls (n=7; 2.39 ± 0.06 mg/g). MW
1K-1C rats (n = 7; BP = 176 ± 15 mmHg) had substantial CH (LV/BW = 3.37 ± 0.2
mg/g). Ramp vagal heart rate (HR)
baroreflexes were measured in conscious, chronically instrumented EX, sedentary
and 1K-1C rats by rapid injection of methoxamine (50-100 mg/kg, i.v) ± ANP infusion
(150 ng/kg/min). ANP enhanced ramp
baroreflex sensitivity in sedentary rats (-0.81 ± 0.2 vs -1.83 ± 0.2 bpm/mmHg; P<0.05) and also in EX rats, despite
their CH (-1.14 ± 0.2 vs -1.70 ± 0.2
bpm/mmHg; P<0.05). Similar to
findings in SHR, 1K-1C rats with CH were insensitive to baroreflex effects of
ANP (-0.80 ± 0.09 (saline) vs -0.75 ±
0.16 (ANP) bpm/mmHg). Whereas CH
resulting from hypertension abolished ANP effects on vagal baroreflexes, CH
caused physiologically did not. Thus, a
factor or process associated with CH, induced by hypertension of any etiology,
inhibits the potentially beneficial (cardioprotective) parasympathetic reflex
actions of ANP.
