Factors involved in the physiological regulation of the cerebral circulation

Summary:The effect of vasoactive peptides on vascular smooth muscle in the cerebral microcirculation was ex amined using an isolated intracerebral arteriole prepara tion. Extraluminally applied vasoactive intestinal peptide (VIP) dilated the spontaneous tone of intracerebral arte rioles to 118.9 ± 3.1% of control diameter at pH 7.30, with an EC50 of 7.27 x 10-8 M. Similar degrees of dila tion to VIP were seen in vessels preconstricted by changing bath solution to pH 7.60. Substance P had no effect on vessel diameter at pH 7.30. However, in vessels precontracted by pH 7.60, significant dose-dependent di lation was observed with an EC50 of 2.55 x 10-1 0 M.Local chemical, neural, and humoral mecha nisms affect cerebral vascular resistance. Neural regulation of cerebral blood flow is mediated by ad renergic, cholinergic, and peptidergic mechanisms. These systems, acting either alone or in combina tion, change vessel caliber and thus change resis tance to blood flow. Adrenergic and cholinergic control of cerebral resistance vessels occurs mainly by the release of a vasoactive substance from nerve endings near the wall of the vessel. Innervation of cerebral vessels has been demonstrated both ana tomically, by histochemical methods, and physio logically by studies of vascular smooth muscle in vitro and studies of CBF regulation in vivo.Some neural responses of the cerebral circula tion, however, are not controlled by the classical 254Neuropeptide Y constricted intracerebral arterioles to 8l.22 ± 2.7% of control diameter, with an EC50 of 6.23 x 10-1 0 M. Bradykinin dilated intracerebral arterioles at pH 7.30 and pH 7.60 to 130 ± 3.0% of control diameter. VIP and bradykinin are potent vasodilators of intracerebral arterioles. Neuropeptide Y is a vasoconstrictor. The ef fect of substance P appeared to be either pH-dependent or dependent on some degree of precontraction by an other agonist, but no effect on vessel diameter was seen at pH 7.30.

Section: Discussion Vasoactive Intestinal Peptide (Vip)mentioning

confidence: 99%

Vasomotor Responses of Rat Intracerebral Arterioles to Vasoactive Intestinal Peptide, Substance P, Neuropeptide Y, and Bradykinin

Dacey

Bassett

Takayasu

1988

“…2) implies that all of the mechanisms that contribute to the hypercapnic increase in CBF must involve NO sensitive pathways. Another mechanism for the hy percapnic increase in CBF could be a "direct" ef fect of CO2 on cerebral arteries due to extracellular acidosis (Kontos et aI., 1977;Busija and Heistad, 1984). This "direct" effect of extracellar acidosis could be mediated by vascular endothelium or peri vascular nerves that contain NOS (Bredt et aI., 1990;Nozaki et aI., 1992).…”

Section: Discussionmentioning

confidence: 99%

“…While part of the increase in cerebral blood flow is mediated through a local vascular reaction to hypercapnic ac idosis (Kontos et aI., 1977;Busija and Heistad, 1984), a number of central neuronal and peripheral neurohormonal factors may also play a role (Shalit et aI., 1967; MacKenzie et aI., 1976; Hemmingsen et aI., 1979; Berntman et aI., 1979; Siesjo et aI., 1980; Reddy et aI., 1986;Bryan, 1990; Dora et aI., 1992).…”

mentioning

confidence: 99%

Role of Nitric Oxide in Regulating Cerebrocortical Oxygen Consumption and Blood Flow during Hypercapnia

Horváth

Sándor

Ruttner

et al. 1994

Summary: The effect of the nitric oxide (NO) synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) on the response of cerebrocortical oxygen consumption (CMR02) and blood flow (CBF) to two levels of hyper capnia (PaC02 -60 mm Hg and Pac02 -90 mm Hg) was investigated in ketamine-anesthetized rats. CBF was cal culated using the Kety-Schmidt approach and CMR02 was calculated from the product of CBF and the arterio venous (superior sagittal sinus) difference for oxygen. L-NAME treatment did not have a significant effect onThe mechanism by which hypercapnia exerts its effect on cerebral blood flow is elusive. While part of the increase in cerebral blood flow is mediated through a local vascular reaction to hypercapnic ac idosis (Kontos et aI., 1977;Busija and Heistad, 1984), a number of central neuronal and peripheral neurohormonal factors may also play a role (Shalit et aI., 1967; MacKenzie et aI., 1976; Hemmingsen et aI., 1979; Berntman et aI., 1979; Siesjo et aI., 1980; Reddy et aI., 1986;Bryan, 1990; Dora et aI., 1992).Nitric oxide (NO) is a recently discovered mes senger molecule that mediates a wide variety of physiological and pathological effects in the cardio vascular, endocrinological, peripheral nervous, and central nervous systems (for reviews see Moncada et aI., 1991;Ignarro, 1991;and Synder, 1992). NO is 503either CMR02 or CBE under normocapnic conditions but inhibited the hypercapnic increase of CMR02 and the hy percapnic increase in CBF. These results suggest that NO plays a role in the response of CMR02 and CBF during hypercapnia and are consistent with the suggestion that at least part of the increase in CBF observed during hyper capnia is coupled to an increase in CMR02•

“…The influence of the sympathetic tone on cerebral blood flow and its autoregulation has been inten sively investigated (Busija and Heistad, 1984). Dur ing electric stimulation of the cervical sympathetic nerves, the limits of CBF autoregulation are shifted to higher blood pressures (Bill and Linder, 1976;Edvinsson et aI., 1976;MacKenzie et aI., 1979).…”

Section: Discussionmentioning

confidence: 99%

Acute Sympathetic Denervation Does Not Eliminate the Effect of Angiotensin Converting Enzyme Inhibition on CBF Autoregulation in Spontaneously Hypertensive Rats

Waldemar

1990

Summary:The effect of angiotensin converting enzyme inhibition with captopril (10 mg/kg i.v.) on CBF autoreg ulation was studied in 16 spontaneously hypertensive rats (8 control and 8 treated with captopril) sUbjected to acute cervical sympathectomy. CBF was measured repetitively by the intra-arterial I33Xe injection method, during the manipulation of MABP by norepinephrine or hemor rhagic hypotension. Prior to the administration of drugs, baseline MABP was 112 ± 10 mm Hg in the control group Although it was speculated that the effect of cap topril was caused by a reduction of the angiotensin II-induced tone in the larger cerebral arteries (Barry et aI., 1984), the mechanism for the observed effect of ACE inhibition on CBF autoregulation remains to be clarified. Since the renin-angiotensin system interacts with the sympathetic nervous system (Zimmerman, 1978), the effect might result from in hibition of cerebrovascular sympathetic tone, rather than direct inhibition of the angiotensin II induced tone in cerebral arteries. In that case, how-