Aging and hypertension differently affect contractility of rat
mesenteric resistance arteries: modulation by endothelium-derived
factors.
Lang, Markus G., Georg Noll, and Thomas F. L[umlaut]uscher.
Department of Research, Laboratory of Vascular Research, University
Hospital Basel and Cardiology, Cardiovascular Research, University
Hospital / Inselspital, CH - 3010 Bern, Switzerland
APStracts 2:0134H, 1995.
The effects of aging and hypertension on contraction were examined in
rat mesenteric resistance arteries of 12 and 74 weeks old Wistar
Kyoto (WKY) and spontaneously hypertensive rats (SHR). The vessels
were suspended in myographs (37 C, 95% O2/5% CO2) filled with
modified Krebs-Ringer Henseleit solution. Isometric tension was
measured. Contractions to KCl (100mM) were similar in adult WKY and
SHR; they increased in senescent WKY (p<0.05), but decreased in
senescent SHR (p<0.05). Responses to norepinephrine (% of KCl) were
comparable in all 4 groups. However, blockade of nitric oxide (NO)
production with L-NAME enhanced the sensitivity to norepinephrine in
senescent animals, particularly in SHR. Inhibition of cyclooxygenase
with indomethacin prevented the increased sensitivity to
norepinephrine after NO blockade. Responses to angiotensin II were
not affected by aging and hypertension, but the thromboxane receptor
antagonist SQ 30741 reduced angiotensin II-induced contractions only
in SHR of both ages (p<0.05). Aging increased responses to
angiotensin I in SHR, but decreased it in WKY (p<0.05). In quiescent
rings with endothelium, acetylcholine caused contractions in the
presence of L-NAME in adult and senescent SHR, but not in WKY
(p<0.05). SQ 30741 prevented these contractions (p<0.05).
Contractions to the thromboxane analogue U 46619 were reduced only in
senescent SHR (p<0.05). Thus, aging increases and hypertension
decreases contractility of smooth muscle in rat mesenteric resistance
arteries. In SHR of both age groups, increased formation of an
endothelium-derived contracting factor, most likely prostaglandin
H2/thromboxane A2, occurs in response to angiotensin II,
acetylcholine and possibly also norepinephrine. Aging enhances ACE
activity in SHR, whereas the contrary occurs in WKY. These changes in
contractility of SHR mesenteric resistance arteries might be
important for the pathophysiology of hypertension.
Received 11 July 1994; accepted in final form 27 March 1995.
APS Manuscript Number H602-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.