Contribution of extrinsic factors and intrinsic vascular alterations to reduced arteriolar reactivity with high-salt diet and hypertension

Objective: To determine whether relaxation of skeletal muscle arterioles of rats on high-salt diet or with reduced renal mass hypertension (RRM-HT) represents intrinsic alterations to microvessels alone, or whether extravascular influences also contribute to reduced dilator responses. Methods: Normotensive (NT) Sprague-Dawley rats were fed low-salt (LS) or high-salt (HS) diets, and RRM-HT rats were fed HT diet for 4-6 weeks. In situ and isolated cremaster muscle first-order arterioles (1A) were examined using television microscopy, and a video micrometer was used to measure diameter changes in response to acetylcholine (ACH), cholera toxin (CT), and sodium nitroprusside (SNP). Results: Compared to normotensive low-salt (NT-LS) rats, responses of 1A to the agonists were reduced in normotensive high-salt (NT-H) and RRM-HT rats. Arteriolar reactivity to the agonists in NT-LS rats and in NT-HS rats was not different between in situ and in vitro environments. However, in RRM-HT rats, the reactivity of 1A to each agonist was greater in isolated arterioles than in in situ arterioles. Conclusions: These results suggest that the impaired response of skeletal muscle arterioles to vasodilator stimuli in normotensive rats on high-salt diet primarily reflects alterations to microvessels alone, while reduced dilator responses in RRM-HT rats represent a combination of extravascular influences and intrinsic alterations to arterioles themselves.