In Situ Small Blood Vessel Electrical Response to Verapamil in Spontaneously Hypertensive Rats
Changes in vascular smooth muscle tone in hypertension — Development of essential hypertension in man and in the genetically altered spontaneously hypertensive rat (SHR) model of this disease is characterized hemodynamically by a transient elevation in cardiac output, a sustained elevation in total peripheral resistance (TPR) and a reduction in venous capacitance (1,2). The results of many investigations indicate that, in addition to pressure mediated structural adaptation on the arterial side of the circulation (3,4), an increased vascular smooth muscle (VSM) tone contributes significantly to the latter two hemodynamic changes. In the SHR model this increase in VSM tone includes an elevated sympathetic efferent input (5,6) which may be the result of an alteration in a central nervous sensing system (7). In addition, defects in the SHR VSM cell membrane mechanisms that regulate intracellular “activator calcium” (Cai) and therefore excitation-contraction coupling have been postulated to explain observed elevated sensitivity to external neurogenic and humoral influences in certain vessels (7,8,9,10). The defects in these membrane regulatory mechanisms and their temporal relation to the development and maintenance of the elevated VSM tone in SHR remain to be established, particularly in the small resistance and capacitance vessels. In addition to transmembrane ionic flux measurements (11,12), two other important parameters that can be used to assess changes in these membrane regulatory mechanisms are the VSM transmembrane potential (Em)(6,13,14) and the contractile force (7,8,9).
Unable to display preview. Download preview PDF.
- 4.Folkow B. Cardiovascular structural adaptation; its role in the initiation and maintenance of primary hypertension. Clin. Sci. Mol. Med. (55): 3s–22s, 1978.Google Scholar
- 5.Yamori Y. Neurogenic mechanisms of spontaneous hypertension. In: Onesti G, Fernandes M, Kim K (Eds) Regulation of Blood Pressure by the CNS, Grune and Stratton, New York, 1976, pp. 65–76.Google Scholar
- 7.Bohr D. What makes the pressure go up? A hypothesis. Hypertension (3) (Suppl): II160-II165, 1981Google Scholar
- 9.Mulvany MJ. Do resistance vessel abnormalities contribute to the elevated blood pressure of spontaneously hypertensive rats? Bloodvessels (20): 1–22, 1983.Google Scholar
- 10.Toggart EJ(Jr), Zelis R. The role of calcium blockers in the treatment of other cardiovascular disorders. In: Flaim SF, Zelis R (eds) Calcium Blockers, Urban and Schwarzenberg, Baltimore-Munich, 1982, pp. 265–283.Google Scholar
- 11.Jones AW. Vascular smooth muscle alterations during hypertension. In: Bulbring E, Brading A, Jones A, Tomita T (eds) Smooth Muscle, Univ. of Texas Press, Austin, 1981, pp. 297–429.Google Scholar
- 13.Stekiel WJ, Contney SJ, Lombard JH, Willems WJ. Effect of adrenergic denervation on small mesenteric vessel membrane potential responses to noradrenaline in spontaneously hypertensive and Wistar-Kyoto rats. In: Rascher W, Clough D, Ganten D (eds) Hypertensive Mechanisms. The SHR as a Model to Study Human Hypertension, Schattauer, New York, 1982, pp. 252–255.Google Scholar
- 14.Hermsmeyer K, Trapani A, Abel PW. Membrane potential-dependent tension in vascular muscle. In: Vanhoutte PM, Leusen I (eds) Vasodilation, Raven Press, New York, 1981, pp. 273–284.Google Scholar
- 16.Stekiel WJ, Contney SJ, Lombard JH, Harder DR. Response of venous membrane potentials to calcium blockade in spontaneous hypertension. Hypertension 5 (Suppl I) 164–169, 1983.Google Scholar
- 18.Johansson B, Somlyo A. Electrophysiology and excitation- contraction coupling. In: Bohr DF, Somlyo AP, Sparks HV (eds) Handbook of Physiology, Sect. 2, Vol. I, Am. Physiol. Soc., Bethesda MD 1980, pp. 301–323.Google Scholar
- 22.Loutzenhizer R, van Breemen C. Mechanisms of stimulated Ca2+ influx and consequences of influx inhibition. In: Merrill GF, Weiss HR (eds). Ca2+Entry Blockers, Adenosine and Neuro-humors, Urban and Schwarzenberg, Baltimore-Munich, 1983, pp. 73–89.Google Scholar
- 23.Flaim SF. Comparative pharmacology of calcium blockers based on studies of vascular smooth muscle. In: Flaim SF, Zelis R (eds) Calcium Blockers, Urban and Schwarzenberg, Baltimore- Munich, 1982, pp. 155–178.Google Scholar
- 26.Noon JP, Rice PJ, Baldessarini RJ. Calcium leakage as a cause of the high resting tension in vascular smooth muscle from the spontaneously hypertensive rat. Proc. Natl. Acad. Sci. USA (75): 605–607, 1975.Google Scholar