Floyd R. Domer

Nitric Oxide Mediates Penile Erection in Cats

The present study was undertaken to investigate the in vivo effects of nitric oxide (NO) mediating agents injected intracavernosally on penile erection in cats. All NO donors increased the cavernosal pressure and penile length in a dose-dependent manner. The maximal effects on cavernosal pressure and penile length induced by s-nitrosocysteine (NO-CYS) and s-nitroso-n-acetylpenicillamine (SNAP), respectively, were 8-fold and 5-fold increases in pressure, and 45% and 34% increases in length when compared with baseline values. These changes were comparable to that caused by the control drug combination (papaverine, phentolamine and prostaglandin E1). The effects of acetylcholine (ACh) and substance P on cavernosal pressure and penile length were less than those obtained with the control drug combination, NO-CYS (p < 0.01), or SNAP (p < 0.05). N omega-nitro-l-arginine-methyl-ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, significantly decreased the effects of NO-CYS, ACh and substance P on penile erection. This in vivo study with NO donors and an NOS inhibitor suggests that NO is a mediator of penile erection in cats.

Cerebral Phospholipid Content and Na+, K+‐ATPase Activity During Ischemia and Postischemic Reperfusion in the Mongolian Gerbil

Abstract: Using bilateral carotid artery occlusion in adult gerbils we examined the effects of ischemia and ischemia/reperfusion on cerebral phospholipid content and Na+, K+‐ATPase (EC 3.6.1.3) activity. In contrast to the large changes in phospholipid content and membrane‐bound enzyme activity that have been observed in liver and heart tissues, we observed relatively small changes in the cerebral content of total phospholipid, phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE) following ischemic intervals of up to 240 min. Following 15 min of ischemia the cerebral content of sphingomyelin (SM) was decreased to <50% of control values but returned to near‐normal levels with longer ischemic periods. Significant decreases in the cerebral content of phosphatidylinositol (PI) and phosphatidic acid (PA) were observed following shorter intervals of ischemia (15–45 min). Na+, K+‐ATPase activity of cerebral homogenates prepared from the brains of gerbils subjected to 30–240 min of ischemia was decreased but significantly different from control activity only after 30 min of ischemia (‐29%, p ≤ 0.05). With the exception of PS, reperfusion for 60 min following 60 min of ischemia resulted in marked increases in cerebral phospholipid content with PC, SM, PI, and PA levels exceeding and PE levels equal to preischemic values. Longer periods of reperfusion (180 min) resulted in decreases in cerebral phospholipid content toward (PC, SM, PI, and PA) or below (PE) preischemic levels. In contrast, the cerebral content of PS significantly decreased during reperfusion (‐51% at 60 min, p ≤ 0.05) and remained below preischemic values even after 180 min of reperfusion. The activity of cerebral Na+, K+‐ATPase increased to values slightly above preischemic values following reperfusion for either 60 or 180 min after 60 min of ischemia. These data show that major differences exist in the responses of neural and nonneural tissues to ischemia and raise important questions concerning the role of changes in membrane structure and function in irreversible ischemic injury.

Characterization of the analgesic activity of ketorolac in mice

The spectrum of analgesic activity of ketorolac tromethamine was evaluated with mice exposed to the hot-plate, tail-flick and writhing tests. Morphine and indomethacin were used as representative opioid and non-steroidal analgesics respectively. Ketorolac in doses of 5 or 7.5 mg/kg i.p. was active as an analgesic in all three of the procedures. In each case, naloxone (0.5 mg/kg i.p.) significantly decreased the analgesic activity of ketorolac. It was suggested that ketorolac might act in part by causing the release of endogenous opioids.

Penile erections induced by vasoactive intestinal peptide and sodium nitroprusside

SummaryThe use of vasoactive intestinal peptide (VIP), sodium nitroprusside (SNP), and the reference combination of papaverine, prostaglandin E1, and phentolamine was studied in 22 adult cats. The maximal erectile response (intracavernous pressure, penile length, and rigidity) was produced by intracavernous injection of a combination of 1.65 mg papaverine, 0.5μg PGE1, and 25μg phentolamine. This combination was considered as “control” in order to compare the effect of other agents. VIP and SNP increased the intracavernous pressure and caused erection in a dose-dependent manner with a maximal response obtained with 5μg VIP or 10μg SNP. The duration of peak erection and the total duration of drug effect were significantly shorter with VIP and SNP than with the reference combination (P<0.01). Epinephrine (30μg) reversed the effects of SNP and significantly shortened the duration of peak action and total effect (P<0.05). This study supports the use of an in vivo feline model for the evaluation of vasoactive agents and demonstrates that the intracavernous injection of either VIP or SNP can induce penile erection in the adult cat.

Effects of diuretics on cerebrospinal fluid formation and potassium movement

Abstract Diuretics are compounds which augment the flow of urine, usually by altering ionic movement across tubular epithelial cells. The present experiments were performed to determine the effects of a number of diuretics upon the rate of formation and movement of potassium into another body fluid, viz. cerebrospinal fluid (CSF). An artificial CSF was perfused through the cerebroventricular system of cats anesthetized with pentobarbital. A saline solution of radioactive potassium (42K) was infused intravenously. Following three CSF collection periods, a diuretic was injected intravenously and three more collections of CSF were made. Aminometrodine, mersalyl-theophylline, hydrochlorothiazide, chlorothiazide, triamterene, ethacrynic acid, and acetazolamide all significantly decreased the rate of CSF formation. Only spironolactone significantly increased the rate of CSF formation. A number of the diuretics significantly altered the movement of 42K into the perfusing CSF, but in a manner which did not parallel their actions on the rate of CSF formation. The processes involved in CSF formation and potassium exchange between plasma and CSF appear to be different and independent.

Selective effects of α-MSH and MIF-1 on the blood-brain barrier

The effects of intravenously-injected α-MSH and MIF-1 (Pro-Leu-Gly-NH2) on the permeability of blood-brain barrier (BBB) to a large protein and a small anion were studied using radioiodinated serum albumin (RISA) and 99mTc-labeled sodium pertechnetate. Ther permeability of the BBB to RISA was unaltered by either peptide. Permeability to the inorganic pertechnetate anion, however, was significantly increased by α-MSH but not by MIF-1 at doses known to evoke EEG and behavioral responses. The peptides did not cause a change in the systemic blood pressure. It is possible, therefore, that at least some CNS effects of peripherally administered peptides are exerted by alteration of the permeability of the BBB to other substances.

Effect of hyperextension-hyperflexion (whiplash) on the function of the blood-brain barrier of rhesus monkeys.

Abstract Fifteen rhesus monkeys were placed in a cart and subjected to a sudden acceleration to administer a whiplash. The intensity of the acceleration of the head was determined either with a high-speed movie or from accelerometers mounted on the skull. The cart was maximally accelerated at 35 g 30 ms after onset of the impact, and the maximal angular acceleration was 40 × 10 3 rad/s 2 at 50 ms. The animals did not apparently lose consciousness. The permeability of the blood-brain barrier (BBB) was assessed prior to and 1 h after the whiplash trauma using intravenously administered radioactive pertechnetate ( 99m Tc). The ratio of radioactivity in the cerebrospinal fluid to that in the blood 1 h after administration served as a measure of the blood-brain barrier permeability. Prior to the whiplash trauma this ratio was 4.85 × 10 −3 , and after the trauma it had increased to 28.44 × 10 −3 . This acute change in barrier function may contribute to the alterations in function of the central nervous system subsequent to whiplash trauma.

Dose-dependent, amphetamine-induced changes in permeability of the blood-brain barrier of normotensive and spontaneously hypertensive rats

The permeability of the blood-brain barrier to 131I-radioiodinated human serum albumin can be changed by the acute administration of amphetamine intravenously. In normotensive rats (WKY), the response was dose dependent and biphasic. The permeability was increased by doses of 7.5 mg/kg or less and the permeability was decreased by doses of 15 and 30 mg/kg. The response to amphetamine in spontaneously hypertensive rats (SHR) was quite different. The permeability of the blood-brain barrier was greater in the saline-treated spontaneously hypertensive animals than in the saline-treated normotensive animals. Doses of amphetamine to as much as 5 mg/kg caused an increase in permeability, but much less than was found in the normotensive animals. At doses of amphetamine from 7.5 to 30 mg/kg, there were no significant changes in permeability of the blood-brain barrier. There was a high correlation between the acute change in blood pressure caused by the administration of amphetamine and the change in permeability of the blood-brain barrier.

Basic physiology of cerebrospinal fluid outflow

The development of the experimental evidence for bulk flow of cerebrospinal fluid (CSF) back into the venous blood at the arachnoid villi is reviewed. A number of physiological experiments indicated that there was a functional channel between the CSF and the blood. Initially, electron microscopic experiments suggested that the arachnoid villi were covered only by intact cellular membranes and the cells were joined by tight junctions. Subsequent reports have presented evidence of functional changes in the membranes of the villi whereby temporary channels are formed through the cell. These channels provide temporary connections between the two body compartments. Also, as pressure increases in the subarachnoid space, the cells of the arachnoid villi thin, the connections between cells separate somewhat, and the number of pinocytotic vesicles formed on the CSF side of the cell increases greatly. The result is an increased bulk flow of CSF into the bloodstream as the pressure in the subarachnoid space increases.

Effects of acute hypertension on the extravasation of macromolecule in the temporal bone — The possible involvement of the blood-inner ear barrier

ZusammenfassungUntersuchungen nach Injektion radioaktiv markierten menschlichen Serumalbumins beim Meerschweinchen zeigen, daß eine Blut-Innenohrbarriere besteht. Diese weist die gleichen Charakteristika auf, wie die Blut-Hirnschranke.SummaryIn guinea pigs the radioactivity in the vascular beds was washed out by a cardiac perfusion of saline 15 min after the injection of 50 μCi of radioiodinated human serum albumin (RISA). The brain and temporal bones were dissected and a blood sample was obtained. To examine the degree of extravasation of RISA, the extravascular radioactivity in the tissues was measured and expressed as a ratio to that of the blood. Intravenous injection of amphetamine sulfate increased the extravasation in the brain and the temporal bone of the rat but did not increase it in either tissue of the guinea pig. It was proposed that this was because amphetamine did not cause the blood pressure of the guinea pig to reach the “critical level” which would cause the opening of the blood-tissue barrier. In the rat the degrees of extravasation in both the brain and the temporal bone paralleled the maximal mean arterial pressure caused by amphetamine. It is proposed on the basis of these data that there may exist a blood-inner ear barrier and that this barrier has the same characteristics as the blood-brain barrier.