Sustained hypertension in Dahl rats. Negative correlation of agonist response to blood pressure.
The perfused mesenteric vasculature of Dahl salt-sensitive rats on a high salt diet for 5 days (prehypertensive or early hypertensive) is selectively supersensitive to norepinephrine. The present goal was to determine whether that supersensitivity was maintained as hypertension developed. Littermates of salt-sensitive and salt-resistant rats (Dahl Brookhaven strain) were followed on low or high salt for up to 6 weeks. Systolic blood pressure was elevated in the salt-sensitive, high salt rats after 3 or 6 weeks but not after 5 days of the diet. The perfused mesenteric vascular beds from salt-sensitive rats were supersensitive to norepinephrine and nerve stimulation but not to potassium chloride when the rats had been maintained for 5 days or 3 weeks on the high salt diet. However, responses to norepinephrine declined after 6 weeks of the high salt diet. To determine whether sustained high blood pressure has a negative effect on mesenteric vascular responses, we conducted additional experiments with perfused mesenteric vascular beds from salt-sensitive Brookhaven (high salt, 5 weeks) and Rapp (high salt, 6 weeks) animals. Both groups exhibited significant negative correlations between in vivo systolic pressure and maximal responses of mesenteric vessels to norepinephrine and potassium chloride. We suggest that sustained hypertension in Dahl rats has a negative effect on the contractility of the mesenteric arterial system that, by 5 to 6 weeks, masks the initial supersensitivity to norepinephrine. No effects of any diet on the dilating responses of the mesenteric vessels to acetylcholine were observed in any group.
Kong
J Q
JQ
Department of Pharmacology and Toxicology, West Virginia University, Robert C. Byrd Health Sciences Center, Morgantown 26506-9223.
Taylor
D A
DA
Fleming
W W
WW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D012965:Sodium Chloride / Q000008:administration & dosage
D012965:Sodium Chloride; D011189:Potassium Chloride; D009638:Norepinephrine