Effect of Age on Noradrenaline Sensitivity of Mesenteric Resistance Vessels in Spontaneously Hypertensive and Wistar—Kyoto Rats

Abstract

1. We have compared the noradrenaline sensitivity of 150 micron arterial resistance vessels taken from a specific place in the mesenteric bed of spontaneously hypertensive (SH) rats and of control Wistar-Kyoto (WK) rats at three ages: 6 weeks, 12 weeks and 24 weeks. 2. The noradrenaline sensitivity of the vessels under normal conditions was the same at all ages in both SH and WK rats (ED50 about 3 mu mol/l). 3. After addition of cocaine (which inhibits the uptake of noradrenaline in the nerve terminals) all vessels became more sensitive to noradrenaline, but at all ages the increase in sensitivity was greater in the vessels of SH rats, suggesting that the smooth muscle cells in these vessels had a greater intrinsic noradrenaline sensitivity than the vessels of WK rats. 4. Since elevation of the blood pressure in the SH rats occurs mainly between the ages of 6 and 12 weeks, the results suggest that the greater intrinsic smooth muscle cell sensitivity of the SH rat vessels is a factor which is amongst the primary factors responsible for the development of hypertension in the SH rat.

Pre- and Post-Junctional Adrenergic Mechanisms and Hypertension

“…It is reduced in the heart of older SH rats (Nykanen, Ahtee, Himberg & Paasonen, 1973;Salt & Iversen, 1973;Gudeska, Glavas, Stojanova, Petrov, Trajkov & Nikodejevic, 1976;Howe, Provis, West & Chalmers, 1979) or rats made hypertensive by adrenergic regeneration, by renal ligature of eight or salt loading (LeLorier, Hedtke & Shideman, 1976), and of renal hypertensive dogs (Lefer & Ayers, 1969); neuronal uptake is also depressed in the aorta and the kidney of DOCA-treated, salt-loaded and renal hypertensive rats, but not of the renal hypertensive dog (Lefer & Ayers, 1969;LeLorier et al, 1976;Fink & Brody, 1978). By contrast, both direct measurements of [3Hlnoradrenaline uptake and studies of the effects of inhibitors of neuronal uptake indicate that the activity of the neuronal amine pump is greater than normal in resistance vessels and arteries of the adult SH rat and of rabbits made hypertensive by partial constriction of the abdominal aorta (Bevan, Purdy, Su & Bevan, 1975;Collis & Vanhoutte, 1977, 1978aMulvany, Lajaer & Christensen, 1979;Webb & Vanhoutte, 1979;Whall, Myers & Halpern, 1980).…”

“…Differences in the distribution of subtypes of peripheral adrenoreceptors may help explain variations in sensitivity to the hypotensive effects of drugs such as clonidine and prazosin among different species and different animal models of hypertension (Dadkar, Aroskar & Dohadwalla, 1979;Cambridge & Greengrass, 1980). The true a-adrenergic sensitivity of vascular smooth muscle from the adult SH rat and the spSH rat is augmented when compared with that from normotensive controls; however, this increased sensitivity can be masked by the more efficient disposition of noradrenaline (Clinesmidt, Geller, Govier & Sjoerdsma, 1970;Haeusler & Haefely, 1970;Hermsmeyer, 1976;Collis & Vanhoutte, 1977;Sutter & Ljung, 1977;Lais & Brody, 1978;Nagaoka, Toyoda & Iwatsuka, 1978;Berecek et al, 1979;Mulvany et al, 1979;Webb & Vanhoutte, 1979;Berecek, Schwertsshlag & Gross, 1980b;Whall et al, 1980).…”

Microvascular pressure, flow, and resistance in spontaneously hypertensive rats.

“…24 a - 42 The variability may be the result of an age factor, since the rats used in this study were still in the developmental stage of hypertension. However, Mulvany et al 43 have shown in isolated mesenteric arterial vessels (150 /Am in diameter) that the EDj,, values of NE, a measure of vascular sensitivity, did not vary within groups of SHR and WKY rats at 6, 12, and 24 weeks of age. Thus, it was of vital interest to determine if there were differences in the sensitivity of arteries to vasoconstrictors and if the elevated vascular resistance could be altered by pharmacologically changing local conditions.…”