Vascular gap junctional communication is increased in mineralocorticoid-salt hypertension.
Cells rely on gap junctions for intercellular communication, which is important for growth and contractility. For example, gap junctional communication in the uterus increases near parturition, with a concomitant increase in oscillatory contractions. Because arterial responsiveness to contractile agonists is increased in hypertension, we tested the hypothesis that gap junctional communication is increased in hypertension. We examined thoracic aortas from deoxycorticosterone acetate (DOCA)-salt hypertensive and sham normotensive rats using isolated tissue baths and Western blotting techniques. The concentration of 5-hydroxytryptamine necessary to produce a threshold response was significantly lower in aortas from DOCA-salt (4 nmol/L) compared with sham (100 nmol/L) rats; this was also true for norepinephrine and KCl. In these same aortas, the appearance of spontaneous oscillatory contractions, which are sensitive to the gap junctional inhibitor heptanol (0.3 mmol/L), was more frequent in DOCA-salt arteries (93% versus 14% in sham). Heptanol (1 mmol/L) normalized the DOCA-salt aortic contraction to 5-hydroxytryptamine to levels similar to those of the response of the sham aorta in the presence of heptanol. Western analyses revealed that the density of connexin43 immunoreactivity, the connexin being a constituent of gap junctions, was found to be threefold more abundant in aortic homogenates of DOCA-salt rats compared with that of sham rats. This finding supports the hypothesis that gap junctional communication is increased in hypertension, at least at the protein level. We speculate that this increase results in a portion of the increased vascular reactivity and appearance of contractile oscillations in vascular smooth muscle.
Watts
S W
SW
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317, USA. wattss@pilot.msu.edu
Webb
R C
RC
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003900:Desoxycorticosterone / Q000633:toxicity*; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D009991:Oscillometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D003900:Desoxycorticosterone; D009638:Norepinephrine