<Originals>Relaxation responses to various drugs in superior mesenteric arteries from stroke-prone spontaneously hypertensive rats, especially in relation to aging

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The spontaneously hypertensive rat (SHR), developed from the normotensive Wistar Kyoto Rat (WKY), is a useful animal model in studies of human essential hypertension, due to the similarity of its symptones to human hypertension. Thus, the hypertensive mechanism of this animal has been widely studied. However, most blood vessel studies have dealt with abnormal responses to vasocontractile agents. The maintenance of blood vessel tone depends on contractile and relaxation responses. It has been reported that SHR hypertension may be due to the reduced response of blood vessel to relaxation agents. But many of those studies were carried out on large vessels, such as the aorta and femoral artery. Also, resistance vessels are more influentical than capacitance vessels in the development or maintenance of hypertension. Thus, in this study, the effect of age on the relaxation response of distal superior mesenteric arteries to relaxing agents was compared in storke-prone SHR (SHRSP) and WKY. Relaxation response to isoproterenol, a sympathetic beta receptor stimulating agent, decreased with age in both SHRSP and WKY, with lower SHRSP values. The relaxation response to isoproterenol almost disappeared in 6 month-old SHRSP. Forskolin, adenylate activator, produced dose-dependent relaxation responses in both SHRSP and WKY. Although the relaxation response of 1.5 month-old SHRSP and WKY did not differ, in 3 month-and 6 month-old rats, SHRSP showed a smaller (though not significant) response. Dibutyryl cyclic AMP failed to induce different relaxation responses in SHRSP and WKY, at any age. Endothelium-derived relaxing factor (EDRF) releasing agents, acetylcholine and histamine induced dose-dependent relaxation responses in both SHRSP and WKY. Although the relaxation response of 1.5 and 3 month old-SHRSP and WKY did not differ, in 6 month-old rats, SHRSP response was lower. A extremely high concentration of acetylcholine induced contarctile response followed by small and transient relaxation response in many 3 and 6 month-old SHRSP but few WKY. Nitroglycerin and nitroprusside, No-containing substances, induced a dose-dependent relaxation response in SHRSP and WKY. Although the relaxation response to those agents did not differ between SHRSP and WKY at 1.5 and 3 month of age, the relaxation response was smaller in 6 month-old SHRSP. The relaxation response to dibutyryl cyclic GMP did not differ between SHRSP and WKY, at any age. The relaxation response to adenosine of 1.5 and 3 month-old SHRSP and WKY did not differ, but was lower in month-old SHRSP. Diltiazem, a Ca antagonist, induced equal dose-dependent relaxation responses in SHRSP and WKY, for all ages. These results suggest that the reduced relaxation response to sympathetic beta receptor stimulating agent plays an important role in the development and/or maintenance of hypertension, and that the reduced EDRF production and/or release is involved in hypertension maintenance. Adenosine, a metabolic product of ATP, may also play a role in sustraining high blood pressure.
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<Originals>Relaxation responses to various drugs in superior mesenteric arteries from stroke-prone spontaneously hypertensive rats, especially in relation to aging

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