Key result
Genetically hypertensive rats exhibited markedly reduced baroreflex gain compared to normotensive controls (-0.17 vs -0.37 beat/min/mmHg), an impairment that persisted despite nitric oxide synthase inhibition.
Why the study?
Does inhibition of nitric oxide or substance P alter baroreflex gain in genetically hypertensive rats compared to normotensive rats?
Does inhibition of nitric oxide or substance P alter baroreflex gain in genetically hypertensive rats compared to normotensive rats?
Absolute Event Rate: -0.17% vs -0.37%
p-value: p=<0.0001
Nitric oxide plays an inhibitory role in the rat arterial baroreflex, but impairment of baroreflex gain in genetically hypertensive rats is not secondary to altered nitric oxide or substance P signaling.
Reduced baroreflex gain in genetic hypertension is nitric oxide-independent; leaves open alternative mechanisms and human translation.
The attenuation of baroreflex gain associated with hereditary hypertension could involve abnormal signalling by nitric oxide or substance P. Baroreflex gain was measured in age-matched male genetically hypertensive (GH) and nonnotensive (N) anaesthetised rats from heart rate changes in response to i.v. phenylephrine or sodium nitroprusside. In subgroups of these animals, nitric oxide synthesis was inhibited using NG-nitro-L-arginine methyl ester (L-NAME, 30 mg x kg(-1) i.v.), substance P transmission was blocked using the antagonist SR 140333 (360 nmoles x kg(-1) i.v.) or substance P release was inhibited with resiniferatoxin (4 doses of 0.3 microg x kg(-1) i.v. at 4 min intervals). Baroreflex gain was markedly reduced in GH compared to N animals (N -0.37 +/- 0.04 beat x min(-1) x mm Hg(-1), GH -0.17 +/- 0.02 beat x min(-1) x mm Hg(-1), p < 0.0001). Inhibition of nitric oxide synthase increased baroreflex gain in each strain, but the inter-strain difference in gain persisted (post-treatment N -0.57 +/- 0.07 beat x min(-1) x mm Hg(-1), GH -0.24 +/- 0.05 beat x min(-1) x mm Hg(-1) (p < 0.001). Blockade of receptors or inhibition of substance P release did not affect gain in either strain. Nitric oxide, but not substance P, appears to play an inhibitory role in the rat arterial baroreflex. Impairment of baroreflex gain in GH rats is not secondary to altered nitric oxide signaling.
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Brady et al. (2002) studied Genetic hypertension (n=44). Nitric oxide synthase inhibition (L-NAME) vs. Baseline / Normotensive controls was evaluated on Baroreflex gain (beat/min/mmHg) (p=<0.0001). Genetically hypertensive rats exhibited markedly reduced baroreflex gain compared to normotensive controls (-0.17 vs -0.37 beat/min/mmHg), an impairment that persisted despite nitric oxide synthase inhibition.
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