EFFECT OF AGING AND HYPERTENSION ON CONTRACTILITY OF RESISTANCE ARTERIES - MODULATION BY ENDOTHELIAL FACTORS

The effects of aging and hypertension on contraction were examined in rat mesenteric resistance arteries of 12- and 74-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). The vessels were suspended in myographs (37 degrees C, 95% O-2-5% CO2) filled with modified Krebs-Ringer bicarbonate solution. Isometric tension was measured. Contractions to KCI (100 mM) 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 KCI) were comparable in all four groups. However, blockade of nitric oxide (NO) production with N-G-nitro-L-arginine methyl ester (L-NAME) enhanced the sensitivity to norepinephrine in senescent animals, particularly in SHR. Inhibition of cyclooxygenase with indomethacin prevented increased sensitivity to norepinephrine after NO blockade. Responses to angiotensin (ANG) II were not affected by aging and hypertension, but the thromboxane receptor antagonist SQ-30741 reduced ANG II-induced contractions only in SHR of both ages (P < 0.05). Aging increased responses to ANG 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 H-2 or thromboxane A(2), occurs in response to ANG II, acetylcholine, and possibly also norepinephrine. Aging enhances angiotensin-converting enzyme 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.